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  • Journals
  • Articles  (9,795)
  • Oxford University Press  (9,795)
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  • Oxford University Press  (9,795)
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  • 1
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    AVIA v2.0: annotation, visualization and impact analysis of genomic variants and genes (2015)
    Oxford University Press
    Details
    Publication Date: 2015-08-08
    Description: : As sequencing becomes cheaper and more widely available, there is a greater need to quickly and effectively analyze large-scale genomic data. While the functionality of AVIA v1.0, whose implementation was based on ANNOVAR, was comparable with other annotation web servers, AVIA v2.0 represents an enhanced web-based server that extends genomic annotations to cell-specific transcripts and protein-level functional annotations. With AVIA’s improved interface, users can better visualize their data, perform comprehensive searches and categorize both coding and non-coding variants. Availability and implementation : AVIA is freely available through the web at http://avia.abcc.ncifcrf.gov . Contact : Hue.Vuong@fnlcr.nih.gov 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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  • 2
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    MultiMeta: an R package for meta-analyzing multi-phenotype genome-wide association studies (2015)
    Oxford University Press
    Details
    Publication Date: 2015-08-08
    Description: : As new methods for multivariate analysis of genome wide association studies become available, it is important to be able to combine results from different cohorts in a meta-analysis. The R package MultiMeta provides an implementation of the inverse-variance-based method for meta-analysis, generalized to an n -dimensional setting. Availability and implementation: The R package MultiMeta can be downloaded from CRAN. Contact: dragana.vuckovic@burlo.trieste.it ; vi1@sanger.ac.uk 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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  • 3
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    Gene Loss Dominates As a Source of Genetic Variation within Clonal Pathogenic Bacterial Species (2015)
    Oxford University Press
    Details
    Publication Date: 2015-08-12
    Description: Some of the most dangerous pathogens such as Mycobacterium tuberculosis and Yersinia pestis evolve clonally . This means that little or no recombination occurs between strains belonging to these species. Paradoxically, although different members of these species show extreme sequence similarity of orthologous genes, some show considerable intraspecies phenotypic variation, the source of which remains elusive. To examine the possible sources of phenotypic variation within clonal pathogenic bacterial species, we carried out an extensive genomic and pan-genomic analysis of the sources of genetic variation available to a large collection of clonal and nonclonal pathogenic bacterial species. We show that while nonclonal species diversify through a combination of changes to gene sequences, gene loss and gene gain, gene loss completely dominates as a source of genetic variation within clonal species. Indeed, gene loss is so prevalent within clonal species as to lead to levels of gene content variation comparable to those found in some nonclonal species that are much more diverged in their gene sequences and that acquire a substantial number of genes horizontally. Gene loss therefore needs to be taken into account as a potential dominant source of phenotypic variation within clonal bacterial species.
    Electronic ISSN: 1759-6653
    Topics: Biology
    Published by Oxford University Press
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  • 4
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    Draft Genomes, Phylogenetic Reconstruction, and Comparative Genomics of Two Novel Cohabiting Bacterial Symbionts Isolated from Frankliniella occidentalis (2015)
    Oxford University Press
    Details
    Publication Date: 2015-08-12
    Description: Obligate bacterial symbionts are widespread in many invertebrates, where they are often confined to specialized host cells and are transmitted directly from mother to progeny. Increasing numbers of these bacteria are being characterized but questions remain about their population structure and evolution. Here we take a comparative genomics approach to investigate two prominent bacterial symbionts (BFo1 and BFo2) isolated from geographically separated populations of western flower thrips, Frankliniella occidentalis. Our multifaceted approach to classifying these symbionts includes concatenated multilocus sequence analysis (MLSA) phylogenies, ribosomal multilocus sequence typing (rMLST), construction of whole-genome phylogenies, and in-depth genomic comparisons. We showed that the BFo1 genome clusters more closely to species in the genus Erwinia, and is a putative close relative to Erwinia aphidicola . BFo1 is also likely to have shared a common ancestor with Erwinia pyrifoliae/Erwinia amylovora and the nonpathogenic Erwinia tasmaniensis and genetic traits similar to Erwinia billingiae . The BFo1 genome contained virulence factors found in the genus Erwinia but represented a divergent lineage. In contrast, we showed that BFo2 belongs within the Enterobacteriales but does not group closely with any currently known bacterial species. Concatenated MLSA phylogenies indicate that it may have shared a common ancestor to the Erwinia and Pantoea genera, and based on the clustering of rMLST genes, it was most closely related to Pantoea ananatis but represented a divergent lineage. We reconstructed a core genome of a putative common ancestor of Erwinia and Pantoea and compared this with the genomes of BFo bacteria. BFo2 possessed none of the virulence determinants that were omnipresent in the Erwinia and Pantoea genera. Taken together, these data are consistent with BFo2 representing a highly novel species that maybe related to known Pantoea .
    Electronic ISSN: 1759-6653
    Topics: Biology
    Published by Oxford University Press
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  • 5
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    Gains and Losses of Transcription Factor Binding Sites in Saccharomyces cerevisiae and Saccharomyces paradoxus (2015)
    Oxford University Press
    Details
    Publication Date: 2015-08-16
    Description: Gene expression evolution occurs through changes in cis - or trans -regulatory elements or both. Interactions between transcription factors (TFs) and their binding sites (TFBSs) constitute one of the most important points where these two regulatory components intersect. In this study, we investigated the evolution of TFBSs in the promoter regions of different Saccharomyces strains and species. We divided the promoter of a gene into the proximal region and the distal region, which are defined, respectively, as the 200-bp region upstream of the transcription starting site and as the 200-bp region upstream of the proximal region. We found that the predicted TFBSs in the proximal promoter regions tend to be evolutionarily more conserved than those in the distal promoter regions. Additionally, Saccharomyces cerevisiae strains used in the fermentation of alcoholic drinks have experienced more TFBS losses than gains compared with strains from other environments (wild strains, laboratory strains, and clinical strains). We also showed that differences in TFBSs correlate with the cis component of gene expression evolution between species (comparing S. cerevisiae and its sister species Saccharomyces paradoxus ) and within species (comparing two closely related S. cerevisiae strains).
    Electronic ISSN: 1759-6653
    Topics: Biology
    Published by Oxford University Press
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  • 6
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    A Genome-Wide Landscape of Retrocopies in Primate Genomes (2015)
    Oxford University Press
    Details
    Publication Date: 2015-08-16
    Description: Gene duplication is a key factor contributing to phenotype diversity across and within species. Although the availability of complete genomes has led to the extensive study of genomic duplications, the dynamics and variability of gene duplications mediated by retrotransposition are not well understood. Here, we predict mRNA retrotransposition and use comparative genomics to investigate their origin and variability across primates. Analyzing seven anthropoid primate genomes, we found a similar number of mRNA retrotranspositions (~7,500 retrocopies) in Catarrhini (Old Word Monkeys, including humans), but a surprising large number of retrocopies (~10,000) in Platyrrhini (New World Monkeys), which may be a by-product of higher long interspersed nuclear element 1 activity in these genomes. By inferring retrocopy orthology, we dated most of the primate retrocopy origins, and estimated a decrease in the fixation rate in recent primate history, implying a smaller number of species-specific retrocopies. Moreover, using RNA-Seq data, we identified approximately 3,600 expressed retrocopies. As expected, most of these retrocopies are located near or within known genes, present tissue-specific and even species-specific expression patterns, and no expression correlation to their parental genes. Taken together, our results provide further evidence that mRNA retrotransposition is an active mechanism in primate evolution and suggest that retrocopies may not only introduce great genetic variability between lineages but also create a large reservoir of potentially functional new genomic loci in primate genomes.
    Electronic ISSN: 1759-6653
    Topics: Biology
    Published by Oxford University Press
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  • 7
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    Cancer, Warts, or Asymptomatic Infections: Clinical Presentation Matches Codon Usage Preferences in Human Papillomaviruses (2015)
    Oxford University Press
    Details
    Publication Date: 2015-08-06
    Description: Viruses rely completely on the hosts’ machinery for translation of viral transcripts. However, for most viruses infecting humans, codon usage preferences (CUPrefs) do not match those of the host. Human papillomaviruses (HPVs) are a showcase to tackle this paradox: they present a large genotypic diversity and a broad range of phenotypic presentations, from asymptomatic infections to productive lesions and cancer. By applying phylogenetic inference and dimensionality reduction methods, we demonstrate first that genes in HPVs are poorly adapted to the average human CUPrefs, the only exception being capsid genes in viruses causing productive lesions. Phylogenetic relationships between HPVs explained only a small proportion of CUPrefs variation. Instead, the most important explanatory factor for viral CUPrefs was infection phenotype, as orthologous genes in viruses with similar clinical presentation displayed similar CUPrefs. Moreover, viral genes with similar spatiotemporal expression patterns also showed similar CUPrefs. Our results suggest that CUPrefs in HPVs reflect either variations in the mutation bias or differential selection pressures depending on the clinical presentation and expression timing. We propose that poor viral CUPrefs may be central to a trade-off between strong viral gene expression and the potential for eliciting protective immune response.
    Electronic ISSN: 1759-6653
    Topics: Biology
    Published by Oxford University Press
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  • 8
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    Gene selection for the reconstruction of stem cell differentiation trees: a linear programming approach (2015)
    Oxford University Press
    Details
    Publication Date: 2015-08-08
    Description: Motivation: Stem cell differentiation is largely guided by master transcriptional regulators, but it also depends on the expression of other types of genes, such as cell cycle genes, signaling genes, metabolic genes, trafficking genes, etc. Traditional approaches to understanding gene expression patterns across multiple conditions, such as principal components analysis or K-means clustering, can group cell types based on gene expression, but they do so without knowledge of the differentiation hierarchy. Hierarchical clustering can organize cell types into a tree, but in general this tree is different from the differentiation hierarchy itself. Methods: Given the differentiation hierarchy and gene expression data at each node, we construct a weighted Euclidean distance metric such that the minimum spanning tree with respect to that metric is precisely the given differentiation hierarchy. We provide a set of linear constraints that are provably sufficient for the desired construction and a linear programming approach to identify sparse sets of weights, effectively identifying genes that are most relevant for discriminating different parts of the tree. Results: We apply our method to microarray gene expression data describing 38 cell types in the hematopoiesis hierarchy, constructing a weighted Euclidean metric that uses just 175 genes. However, we find that there are many alternative sets of weights that satisfy the linear constraints. Thus, in the style of random-forest training, we also construct metrics based on random subsets of the genes and compare them to the metric of 175 genes. We then report on the selected genes and their biological functions. Our approach offers a new way to identify genes that may have important roles in stem cell differentiation. Contact: tperkins@ohri.ca Supplementary information: Supplementary data are available at Bioinformatics online.
    Print ISSN: 1367-4803
    Electronic ISSN: 1460-2059
    Topics: Biology , Computer Science , Medicine
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  • 9
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    Applying stability selection to consistently estimate sparse principal components in high-dimensional molecular data (2015)
    Oxford University Press
    Details
    Publication Date: 2015-08-08
    Description: Motivation: Principal component analysis (PCA) is a basic tool often used in bioinformatics for visualization and dimension reduction. However, it is known that PCA may not consistently estimate the true direction of maximal variability in high-dimensional, low sample size settings, which are typical for molecular data. Assuming that the underlying signal is sparse, i.e. that only a fraction of features contribute to a principal component (PC), this estimation consistency can be retained. Most existing sparse PCA methods use L1-penalization, i.e. the lasso , to perform feature selection. But, the lasso is known to lack variable selection consistency in high dimensions and therefore a subsequent interpretation of selected features can give misleading results. Results: We present S4VDPCA, a sparse PCA method that incorporates a subsampling approach, namely stability selection. S4VDPCA can consistently select the truly relevant variables contributing to a sparse PC while also consistently estimate the direction of maximal variability. The performance of the S4VDPCA is assessed in a simulation study and compared to other PCA approaches, as well as to a hypothetical oracle PCA that ‘knows’ the truly relevant features in advance and thus finds optimal, unbiased sparse PCs. S4VDPCA is computationally efficient and performs best in simulations regarding parameter estimation consistency and feature selection consistency. Furthermore, S4VDPCA is applied to a publicly available gene expression data set of medulloblastoma brain tumors. Features contributing to the first two estimated sparse PCs represent genes significantly over-represented in pathways typically deregulated between molecular subgroups of medulloblastoma. Availability and implementation: Software is available at https://github.com/mwsill/s4vdpca . Contact: m.sill@dkfz.de 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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  • 10
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    GS-align for glycan structure alignment and similarity measurement (2015)
    Oxford University Press
    Details
    Publication Date: 2015-08-08
    Description: Motivation: Glycans play critical roles in many biological processes, and their structural diversity is key for specific protein-glycan recognition. Comparative structural studies of biological molecules provide useful insight into their biological relationships. However, most computational tools are designed for protein structure, and despite their importance, there is no currently available tool for comparing glycan structures in a sequence order- and size-independent manner. Results: A novel method, GS-align, is developed for glycan structure alignment and similarity measurement. GS-align generates possible alignments between two glycan structures through iterative maximum clique search and fragment superposition. The optimal alignment is then determined by the maximum structural similarity score, GS-score, which is size-independent. Benchmark tests against the Protein Data Bank (PDB) N -linked glycan library and PDB homologous/non-homologous N -glycoprotein sets indicate that GS-align is a robust computational tool to align glycan structures and quantify their structural similarity. GS-align is also applied to template-based glycan structure prediction and monosaccharide substitution matrix generation to illustrate its utility. Availability and implementation: http://www.glycanstructure.org/gsalign . Contact: wonpil@ku.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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