Publications (8)62.12 Total impact
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Article: Comparing thousands of circular genomes using the CGView Comparison Tool.
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ABSTRACT: Continued sequencing efforts coupled with advances in sequencing technology will lead to the completion of a vast number of small genomes. Whole-genome comparisons represent an important part of the analysis of any new genome sequence, as they can provide a better understanding of the biology and evolution of the source organism. Visualization of the results is important, as it allows information from a variety of sources to be integrated and interpreted. However, existing graphical comparison tools lack features needed for efficiently comparing a new genome to hundreds or thousands of existing sequences. Moreover, existing tools are limited in terms of the types of comparisons that can be performed, the extent to which the output can be customized, and the ease with which the entire process can be automated. The CGView Comparison Tool (CCT) is a package for visually comparing bacterial, plasmid, chloroplast, or mitochondrial sequences of interest to existing genomes or sequence collections. The comparisons are conducted using BLAST, and the BLAST results are presented in the form of graphical maps that can also show sequence features, gene and protein names, COG (Clusters of Orthologous Groups of proteins) category assignments, and sequence composition characteristics. CCT can generate maps in a variety of sizes, including 400 Megapixel maps suitable for posters. Comparisons can be conducted within a particular species or genus, or all available genomes can be used. The entire map creation process, from downloading sequences to redrawing zoomed maps, can be completed easily using scripts included with the CCT. User-defined features or analysis results can be included on maps, and maps can be extensively customized. To simplify program setup, a CCT virtual machine that includes all dependencies preinstalled is available. Detailed tutorials illustrating the use of CCT are included with the CCT documentation. CCT can be used to visually compare a reference sequence to thousands of existing genomes or sequence collections (next-generation sequencing reads for example) on a standard desktop computer. It provides analysis and visualization functionality not available in any existing circular genome visualization tool. By visually presenting sequence conservation information along with functional classifications and sequence composition characteristics, CCT can be a useful tool for identifying rapidly evolving or novel sequences, horizontally transferred sequences, or unusual functional properties in newly sequenced genomes. CCT is freely available for download at http://stothard.afns.ualberta.ca/downloads/CCT/.BMC Genomics 05/2012; 13:202. · 4.07 Impact Factor -
Article: In-depth annotation of SNPs arising from resequencing projects using NGS-SNP.
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ABSTRACT: NGS-SNP is a collection of command-line scripts for providing rich annotations for SNPs identified by the sequencing of whole genomes from any organism with reference sequences in Ensembl. Included among the annotations, several of which are not available from any existing SNP annotation tools, are the results of detailed comparisons with orthologous sequences. These comparisons can, for example, identify SNPs that affect conserved residues, or alter residues or genes linked to phenotypes in another species. NGS-SNP is available both as a set of scripts and as a virtual machine. The virtual machine consists of a Linux operating system with all the NGS-SNP dependencies pre-installed. The source code and virtual machine are freely available for download at http://stothard.afns.ualberta.ca/downloads/NGS-SNP/. stothard@ualberta.ca Supplementary data are available at Bioinformatics online.Bioinformatics 06/2011; 27(16):2300-1. · 5.47 Impact Factor -
Article: The genome sequence of taurine cattle: a window to ruminant biology and evolution.
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ABSTRACT: To understand the biology and evolution of ruminants, the cattle genome was sequenced to about sevenfold coverage. The cattle genome contains a minimum of 22,000 genes, with a core set of 14,345 orthologs shared among seven mammalian species of which 1217 are absent or undetected in noneutherian (marsupial or monotreme) genomes. Cattle-specific evolutionary breakpoint regions in chromosomes have a higher density of segmental duplications, enrichment of repetitive elements, and species-specific variations in genes associated with lactation and immune responsiveness. Genes involved in metabolism are generally highly conserved, although five metabolic genes are deleted or extensively diverged from their human orthologs. The cattle genome sequence thus provides a resource for understanding mammalian evolution and accelerating livestock genetic improvement for milk and meat production.Science 05/2009; 324(5926):522-8. · 31.20 Impact Factor -
Article: The CGView Server: a comparative genomics tool for circular genomes.
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ABSTRACT: The CGView Server generates graphical maps of circular genomes that show sequence features, base composition plots, analysis results and sequence similarity plots. Sequences can be supplied in raw, FASTA, GenBank or EMBL format. Additional feature or analysis information can be submitted in the form of GFF (General Feature Format) files. The server uses BLAST to compare the primary sequence to up to three comparison genomes or sequence sets. The BLAST results and feature information are converted to a graphical map showing the entire sequence, or an expanded and more detailed view of a region of interest. Several options are included to control which types of features are displayed and how the features are drawn. The CGView Server can be used to visualize features associated with any bacterial, plasmid, chloroplast or mitochondrial genome, and can aid in the identification of conserved genome segments, instances of horizontal gene transfer, and differences in gene copy number. Because a collection of sequences can be used in place of a comparison genome, maps can also be used to visualize regions of a known genome covered by newly obtained sequence reads. The CGView Server can be accessed at http://stothard.afns.ualberta.ca/cgview_server/Nucleic Acids Research 08/2008; 36(Web Server issue):W181-4. · 8.03 Impact Factor -
Article: Identification of a novel immunosubversion mechanism mediated by a virologue of the B-lymphocyte receptor TACI.
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ABSTRACT: TACI (transmembrane activator and calcium modulator and cyclophilin ligand [CAML] interactor) is a part of a novel network of ligands and receptors involved in B-cell survival and isotype switching. The TACI protein mediates its effects through CAML, an endoplasmic reticulum (ER)-localized protein that controls Ca(2+) efflux. The adenovirus E3-6.7K protein prevents inflammatory responses and also confers resistance from a variety of apoptotic stimuli and maintains ER Ca(2+) homeostasis; however, the mechanism of action is unknown. Here, we provide evidence that E3-6.7K shares sequence homology with TACI and inhibits apoptosis and ER Ca(2+) efflux through an interaction with CAML, a Ca(2+)-modulating protein. We demonstrate a direct interaction between E3-6.7K and CAML and reveal that the two proteins colocalize in an ER-like compartment. Furthermore, the interaction between the two proteins is localized to the N-terminal domain of CAML and to a 22-amino-acid region near the C terminus of E3-6.7K termed the CAML-binding domain (CBD). Mutational analysis of the CBD showed that an interaction with CAML is required for E3-6.7K to inhibit thapsigargin-induced apoptosis and ER Ca(2+) efflux. E3-6.7K appears to be the first virologue of TACI to be identified. It targets CAML in a novel immunosubversive mechanism to alter ER Ca(2+) homeostasis, which consequently inhibits inflammation and protects infected cells from apoptosis.Clinical and Vaccine Immunology 08/2007; 14(7):907-17. · 2.55 Impact Factor -
Article: The adenovirus E3-6.7K protein adopts diverse membrane topologies following posttranslational translocation.
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ABSTRACT: The E3 region of adenovirus codes for several membrane proteins, most of which are involved in immune evasion and prevention of host cell apoptosis. We explored the topology and targeting mechanisms of E3-6.7K, the most recently described member of this group, by using an in vitro translation system supplemented with microsomes. Here, we present evidence that E3-6.7K, one of the smallest signal-anchor proteins known, translocates across the membrane of the endoplasmic reticulum in a posttranslational, ribosome-independent, yet ATP-dependent manner, reminiscent of the translocation of tail-anchored proteins. Our analysis also demonstrated that E3-6.7K could achieve several distinct topological fates. In addition to the previously postulated type III orientation (N-luminal/C-cytoplasmic, termed NtmE3-6.7K), we detected a tail-anchored form adopting the opposite orientation (N-cytoplasmic/C-luminal, termed CtmE3-6.7K) as well as the possibility of a fully translocated form (N and C termini are both translocated, termed NCE3-6.7K). Due to the translocation of a positively charged domain, both the CtmE3-6.7K and NCE3-6.7K topologies of E3-6.7K constitute exceptions to the "positive inside" rule. The NtmE3-6.7K and NCE3-6.7K are the first examples of posttranslationally translocated proteins in higher eukaryotes that are not tail anchored. Distinct topological forms were also found in transfected cells, as both N and C termini of E3-6.7K were detected on the extracellular surface of transfected cells. The demonstration of unexpected topological forms and translocation mechanisms for E3-6.7K defies conventional thinking about membrane protein topogenesis and advises that both the mode of targeting and topology of signal-anchor proteins should be determined experimentally.Journal of Virology 02/2004; 78(1):454-63. · 5.40 Impact Factor -
Article: Adenovirus E3-6.7K maintains calcium homeostasis and prevents apoptosis and arachidonic acid release.
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ABSTRACT: E3-6.7K is a small and hydrophobic membrane glycoprotein encoded by the E3 region of subgroup C adenovirus. Recently, E3-6.7K has been shown to be required for the downregulation of tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) receptors by the adenovirus E3/10.4K and E3/14.5K complex of proteins. We demonstrate here that E3-6.7K has additional protective roles, independent of other virus proteins. In transfected Jurkat T-cell lymphoma cells, E3-6.7K was found to maintain endoplasmic reticulum-Ca(2+) homeostasis and inhibit the induction of apoptosis by thapsigargin. The presence of E3-6.7K also lead to a reduction in the TNF-induced release of arachidonic acid from transfected U937 human histiocytic lymphoma cells. In addition, E3-6.7K protected cells against apoptosis induced through Fas, TNF receptor, and TRAIL receptors. Therefore, E3-6.7K confers a wide range of protective effects against both Ca(2+) flux-induced and death receptor-mediated apoptosis.Journal of Virology 03/2002; 76(4):1578-87. · 5.40 Impact Factor -
Article: A first generation whole genome RH map of the river buffalo with comparison to domestic cattle
Top co-authors
Top Journals
- Journal of Virology (2)
- Science (1)
- Nucleic Acids Research (1)
- Bioinformatics (1)
- BMC Genomics (1)
Institutions
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2008–2012
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University of Alberta
- Department of Agricultural, Food, and Nutritional Science
Edmonton, Alberta, Canada
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2002–2007
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University of British Columbia - Vancouver
- • Department of Microbiology and Immunology
- • Biomedical Research Centre (BRC)
Vancouver, British Columbia, Canada
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