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Search Results: 1 - 10 of 1804 matches for " Volker Brendel "
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MetWAMer: eukaryotic translation initiation site prediction
Michael E Sparks, Volker Brendel
BMC Bioinformatics , 2008, DOI: 10.1186/1471-2105-9-381
Abstract: MetWAMer currently implements five distinct methods for TIS prediction, the most accurate of which is a routine that combines weighted, signal-based translation initiation site scores and the contrast in coding potential of sequences flanking TISs using a perceptron. Also, our program implements clustering capabilities through use of the k-medoids algorithm, thereby enabling cluster-specific TIS parameter utilization. In practice, our static weight array matrix-based indexing method for parameter set lookup can be used with good results in data sets exhibiting moderate levels of 5'-complete coverage.We demonstrate that improvements in statistically-based models for TIS prediction can be achieved by taking the class of each potential start-methionine into account pending certain testing conditions, and that our perceptron-based model is suitable for the TIS identification task. MetWAMer represents a well-documented, extensible, and freely available software system that can be readily re-trained for differing target applications and/or extended with existing and novel TIS prediction methods, to support further research efforts in this area.Translation initiation in eukaryotic mRNA molecules typically follows the basic mechanism postulated by the scanning hypothesis [1], according to which the 40S ribosomal subunit binds to the 5'-cap of an mRNA, scans in the 5' → 3' direction until the first AUG is encountered, stalls to recruit the 60S subunit, and forms the 80S ribosomal particle, which then proceeds unencumbered with translation to render a protein product (reviewed in [2]). Roughly 10% of eukaryotic transcripts are subject to so-called leaky scanning [3], in which the ribosome continues scanning beyond the first AUG codon until it encounters one in a more favorable context [4]. Alternative methods to initiate translation from certain RNAs of viral origin exist, including, one, the formation of kissing stem-loops to facilitate translation initiation from a 5'-proxi
Comparative genomics of Arabidopsis and maize: prospects and limitations
Volker Brendel, Stefan Kurtz, Virginia Walbot
Genome Biology , 2002, DOI: 10.1186/gb-2002-3-3-reviews1005
Abstract: Maize (Zea mays L., corn) was domesticated in the highlands of Central Mexico approximately 10,000 years ago [1]. Corn agriculture spread rapidly into diverse climate zones, ranging from 45° N to 45° S, and supported vast Native American civilizations. Today, maize is one of the world's most important crops: for direct human consumption, as a key component of animal feed, and as the source of chemical feed stocks. Grass species (including maize) cover 20% of the terrestrial surface of the earth, and the grains from maize, rice, wheat, and minor grass crops provide the majority of calories in the human diet [2].Since the beginning of the twentieth century, maize has been a model species for genetic analysis, reflecting its unusual biological features. Maize plants produce separate male and female inflorescences, which greatly facilitates experimentally controlled pollination by eliminating the need for emasculation (Figure 1). Large numbers of progeny (300-600 kernels per ear) and the ease of crossing allow a single maize geneticist to generate more than 100,000 outcross progeny per day. Individual plants produce up to 107 pollen grains, allowing fine-structural genetic mapping for phenotypes that can be scored at the pollen stage. Using this abundant material and extraordinary natural diversity, early geneticists mapped many genes, uncovered subtle genetic phenomena such as paramutation and imprinting, and made practical contributions to agriculture through the discovery of hybrid vigor and cytoplasmic male sterility.The beautiful detail evident in meiotic maize chromosomes stimulated a generation of gifted cytogeneticists to identify the physical basis for recombination, to construct linkage maps tied to chromosomes, and to analyze the consequences of chromosome breakage. Of particular importance to current functional genomics was Barbara McClintock's discovery of transposable elements by analyzing the regulation of somatic variegation and germinal mutation in maiz
The ASRG database: identification and survey of Arabidopsis thaliana genes involved in pre-mRNA splicing
Bing-Bing Wang, Volker Brendel
Genome Biology , 2004, DOI: 10.1186/gb-2004-5-12-r102
Abstract: Most eukaryotic genes contain introns that are spliced from the precursor mRNA (pre-mRNA). The correct interpretation of splicing signals is essential to generate authentic mature mRNAs that yield correct translation products. As an important post-transcriptional mechanism, gene function can be controlled at the level of splicing through the production of different mRNAs from a single pre-mRNA (reviewed in [1]). The general mechanism of splicing has been well studied in human and yeast systems and is largely conserved between these organisms. Plant RNA splicing mechanisms remain comparatively poorly understood, due in part to the lack of an in vitro plant splicing system. Although the splicing mechanisms in plants and animals appear to be similar overall, incorrect splicing of plant pre-mRNAs in mammalian systems (and vice versa) suggests that there are plant-specific characteristics, resulting from coevolution of splicing factors with the signals they recognize or from the requirement for additional splicing factors (reviewed in [2,3]).Genome projects are accelerating research on splicing. For example, with the majority of splicing-related genes already known in human and budding yeast, these gene sequences were used to query the Drosophila and fission yeast genomes in an effort to identify potential homologs [4,5]. Most of the known genes were found to have homologs in both Drosophila and fission yeast. The availability of the near-complete genome of Arabidopsis thaliana [6] provides the foundation for the simultaneous study of all the genes involved in particular plant structures or physiological processes. For example, Barakat et al. [7] identified and mapped 249 genes encoding ribosomal proteins and analyzed gene number, chromosomal location, evolutionary history (including large-scale chromosomal duplications) and expression of those genes. Beisson et al. [8] catalogued all genes involved in acyl lipid metabolism. Wang et al. [9] surveyed more than 1,000 Arabi
Tracembler – software for in-silico chromosome walking in unassembled genomes
Qunfeng Dong, Matthew D Wilkerson, Volker Brendel
BMC Bioinformatics , 2007, DOI: 10.1186/1471-2105-8-151
Abstract: Tracembler takes one or multiple DNA or protein sequence(s) as input to the NCBI Trace Archive BLAST engine to identify matching sequence reads from a species of interest. The BLAST searches are carried out recursively such that BLAST matching sequences identified in previous rounds of searches are used as new queries in subsequent rounds of BLAST searches. The recursive BLAST search stops when either no more new matching sequences are found, a given maximal number of queries is exhausted, or a specified maximum number of rounds of recursion is reached. All the BLAST matching sequences are then assembled into contigs based on significant sequence overlaps using the CAP3 program. We demonstrate the validity of the concept and software implementation with an example of successfully recovering a full-length Chrm2 gene as well as its upstream and downstream genomic regions from Rattus norvegicus reads. In a second example, a query with two adjacent Medicago truncatula genes as seeds resulted in a contig that likely identifies the microsyntenic homologous soybean locus.Tracembler streamlines the process of recursive database searches, sequence assembly, and gene identification in resulting contigs in attempts to identify homologous loci of genes of interest in species with emerging whole genome shotgun reads. A web server hosting Tracembler is provided at http://www.plantgdb.org/tool/tracembler/ webcite, and the software is also freely available from the authors for local installations.Comparative genomics is based on the identification and alignment of homologous genes across multiple species and has become a standard, powerful approach in molecular biology for many purposes, including characterization of structurally and functionally important motifs in gene families. Typically, this approach starts with a set of query sequences as input to sequence similarity-based database search programs such as BLAST [1] to identify significantly similar matches in the sequence dat
ParsEval: parallel comparison and analysis of gene structure annotations
Standage Daniel S,Brendel Volker P
BMC Bioinformatics , 2012, DOI: 10.1186/1471-2105-13-187
Abstract: Background Accurate gene structure annotation is a fundamental but somewhat elusive goal of genome projects, as witnessed by the fact that (model) genomes typically undergo several cycles of re-annotation. In many cases, it is not only different versions of annotations that need to be compared but also different sources of annotation of the same genome, derived from distinct gene prediction workflows. Such comparisons are of interest to annotation providers, prediction software developers, and end-users, who all need to assess what is common and what is different among distinct annotation sources. We developed ParsEval, a software application for pairwise comparison of sets of gene structure annotations. ParsEval calculates several statistics that highlight the similarities and differences between the two sets of annotations provided. These statistics are presented in an aggregate summary report, with additional details provided as individual reports specific to non-overlapping, gene-model-centric genomic loci. Genome browser styled graphics embedded in these reports help visualize the genomic context of the annotations. Output from ParsEval is both easily read and parsed, enabling systematic identification of problematic gene models for subsequent focused analysis. Results ParsEval is capable of analyzing annotations for large eukaryotic genomes on typical desktop or laptop hardware. In comparison to existing methods, ParsEval exhibits a considerable performance improvement, both in terms of runtime and memory consumption. Reports from ParsEval can provide relevant biological insights into the gene structure annotations being compared. Conclusions Implemented in C, ParsEval provides the quickest and most feature-rich solution for genome annotation comparison to date. The source code is freely available (under an ISC license) at http://parseval.sourceforge.net/.
xGDB: open-source computational infrastructure for the integrated evaluation and analysis of genome features
Shannon D Schlueter, Matthew D Wilkerson, Qunfeng Dong, Volker Brendel
Genome Biology , 2006, DOI: 10.1186/gb-2006-7-11-r111
Abstract: Computational infrastructure is vital for all aspects of genome research. The assembled genomic sequence of an organism provides a natural scaffold for organizing biologic data. However, researchers are easily overwhelmed if they do not have the computational tools necessary to interpret the features of these assemblies [1-4]. Although a large number of useful tools are available, they exist primarily as ad hoc collections [5-7]. The xGDB software was designed to provide a framework for genomic data storage, display and analysis, and to provide integration of existing and novel genome analysis tools. The software is portable and easily installed for either public access or as a private workbench. It comes ready to use with the following features and capabilities: detailed feature record pages; detailed views of genomic contexts; support for online community annotation; utilities for storage of feature data in relational databases; effortless integration and attachment of analysis tools; transcript view, which is a novel nucleotide resolution view of genomic contexts; compressed storage and dynamic retrieval of feature evidence alignments; attachment and organization of multiple URLs to any feature in any context; and integrated heuristic searches based on feature identifier, alias, and/or description.It is important to note that xGDB differs from and is complementary to database systems such as GMOD [8], EnsEMBL [9], and GenBank [10]. Unlike these systems, which are tasked to provide encompassing data storage, xGDB instances are applied to specific research oriented tasks, which are enabled by the browser and integrated analysis tools. Because of the varying reliability of genomic features, there is a strong need to go beyond simply plotting such features for display (as would be available in GBrowse [8], for example). Contextual analysis of genomic features often requires filtering each feature by criteria specific to an individual user's needs. Such filtering requ
yrGATE: a web-based gene-structure annotation tool for the identification and dissemination of eukaryotic genes
Matthew D Wilkerson, Shannon D Schlueter, Volker Brendel
Genome Biology , 2006, DOI: 10.1186/gb-2006-7-7-r58
Abstract: Complete and accurate gene structure annotation is a prerequisite for the success of many types of genomic projects. For example, gene expression studies based on gene probes would be misleading unless the gene probes uniquely labelled distinct genes. Identification of potential transcription signals relies on correct determination of transcriptional start and termination sites. Characterization of orthologs or paralogs and other studies of molecular phylogeny are also compromised by incomplete or inaccurate gene structure annotation.Gene structure determination is particularly difficult for eukaryotic genomes. Here, we focus on protein-coding genes. In higher eukaryotes, most of these genes contain introns, and a large fraction of the genes appear to permit alternative splicing [1-3]. High-throughput computational gene structure annotation has been highly successful in providing a first glimpse of the gene content of a genome, but current methods fall short of the goal of complete and accurate gene structure annotation (for example, [4-6]). Recent research has focused on improving prediction sensitivity and specificity by combining multiple sources of evidence [7-9]. However, complexities of transcription and pre-mRNA processing, such as introns in non-coding regions, non-canonical splice sites, and utilization of alternative splice sites, still pose formidable challenges for merely computational methods. Re-annotation efforts for most eukaryotic model genomes have, therefore, relied in large part on manual inspection of gene structure evidence [5,10,11]. However, manual annotation also has shortcomings, such as being typically time-consuming, having exclusive participation, and providing annotations only intermittently [4,10,12].A policy of 'open annotation', using the internet as the forum for annotation, and bringing annotation into the mainstream has been suggested as a means to eliminate the restraints of manual annotation and to develop high quality gene anno
Cross-species EST alignments reveal novel and conserved alternative splicing events in legumes
Bing-Bing Wang, Mike O'Toole, Volker Brendel, Nevin D Young
BMC Plant Biology , 2008, DOI: 10.1186/1471-2229-8-17
Abstract: Based on cognate EST alignments alone, the observed frequency of alternatively spliced genes is lower in Mt (~10%, 1,107 genes) and Lj (~3%, 92 genes) than in Arabidopsis and rice (both around 20%). However, AS frequencies are comparable in all four species if EST levels are normalized. Intron retention is the most common form of AS in all four plant species (~50%), with slightly lower frequency in legumes compared to Arabidopsis and rice. This differs notably from vertebrates, where exon skipping is most common. To uncover additional AS events, we aligned ESTs from other legume species against the Mt genome sequence. In this way, 248 additional Mt genes were predicted to be alternatively spliced. We also identified 22 AS events completely conserved in two or more plant species.This study extends the range of plant taxa shown to have high levels of AS, confirms the importance of intron retention in plants, and demonstrates the utility of using ESTs from related species in order to identify novel and conserved AS events. The results also indicate that the frequency of AS in plants is comparable to that observed in mammals. Finally, our results highlight the importance of normalizing EST levels when estimating the frequency of alternative splicing.Alternative splicing (AS) is an important cellular process that leads to multiple mRNA isoforms from a single pre-mRNA in eukaryotic organisms. Plant AS events used to be regarded as rare. However, a growing number of computational studies have now demonstrated that the frequency of alternatively spliced genes in plants is higher than previously estimated [1,2]. 20–30% of expressed genes are alternatively spliced in Arabidopsis thaliana (At) and rice (Oryza sativa, Os) as revealed by large scale EST-genome alignments [1,2]. A recent study using EST pairs gapped alignments (EST-EST) surveyed 11 plant species and suggested that overall AS frequencies vary greatly in different plant species, with some rates comparable to those
Single Nucleotide Polymorphisms of Human STING Can Affect Innate Immune Response to Cyclic Dinucleotides
Guanghui Yi, Volker P. Brendel, Chang Shu, Pingwei Li, Satheesh Palanathan, C. Cheng Kao
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0077846
Abstract: The STING (stimulator of interferon genes) protein can bind cyclic dinucleotides to activate the production of type I interferons and inflammatory cytokines. The cyclic dinucleotides can be bacterial second messengers c-di-GMP and c-di-AMP, 3’5’-3’5’ cyclic GMP-AMP (3’3’ cGAMP) produced by Vibrio cholerae and metazoan second messenger 2’5’-3’5’ Cyclic GMP-AMP (2’3’ cGAMP). Analysis of single nucleotide polymorphism (SNP) data from the 1000 Genome Project revealed that R71H-G230A-R293Q (HAQ) occurs in 20.4%, R232H in 13.7%, G230A-R293Q (AQ) in 5.2%, and R293Q in 1.5% of human population. In the absence of exogenous ligands, the R232H, R293Q and AQ SNPs had only modest effect on the stimulation of IFN-β and NF-κB promoter activities in HEK293T cells, while HAQ had significantly lower intrinsic activity. The decrease was primarily due to the R71H substitution. The SNPs also affected the response to the cyclic dinucleotides. In the presence of c-di-GMP, the R232H variant partially decreased the ability to activate IFN-βsignaling, while it was defective for the response to c-di-AMP and 3’3’ cGAMP. The R293Q dramatically decreased the stimulatory response to all bacterial ligands. Surprisingly, the AQ and HAQ variants maintained partial abilities to activate the IFN-β signaling in the presence of ligands due primarily to the G230A substitution. Biochemical analysis revealed that the recombinant G230A protein could affect the conformation of the C-terminal domain of STING and the binding to c-di-GMP. Comparison of G230A structure with that of WT revealed that the conformation of the lid region that clamps onto the c-di-GMP was significantly altered. These results suggest that hSTING variation can affect innate immune signaling and that the common HAQ haplotype expresses a STING protein with reduced intrinsic signaling activity but retained the ability to response to bacterial cyclic dinucleotides.
Genome-wide mutagenesis of Zea mays L. using RescueMu transposons
John Fernandes, Qunfeng Dong, Bret Schneider, Darren J Morrow, Guo-Ling Nan, Volker Brendel, Virginia Walbot
Genome Biology , 2004, DOI: 10.1186/gb-2004-5-10-r82
Abstract: MuDR/Mu transposable elements are widely used for mutagenesis and as tags for gene cloning in maize [1,2]. The high efficiency of Mu insertional mutagenesis regulated by MuDR in highly active Mutator lines reflects four features of this transposon family. First, a plant typically has 10-50 copies of the mobile Mu elements [3], although some plants have over 100 copies. Second, they insert late in the maize life cycle, generating diverse mutant alleles transmitted in the gametes of an individual Mutator plant [1]. Third, they exhibit a high preference for insertion into genes [1]. And fourth, most maize genes are targets as judged by the facile recovery of Mu insertion alleles in targeted screens [1,4-6]. In directed tagging experiments, the frequency of Mu-induced mutations for a chosen target gene is 10-3-10-5 [7]. Interestingly, a bronze1 exon [8] and the 5' untranslated region of glossy8 [9] contain hotspots for Mu insertion in specific regions, which may explain the higher frequency of mutable allele recovery for these genes.Somatic mutability, visualized as revertant sectors on a mutant background, is indicative of transposon mobility. By monitoring maintenance of a mutable phenotype, it was established that the Mutator transposon system is subject to abrupt epigenetic silencing, which affects some individuals in most families [10,11]. A molecular hallmark of silencing is that both the non-autonomous Mu elements and the regulatory MuDR element become hypermethylated [12,13]. Without selection for somatic instability of a visible reporter allele and/or hypo-methylation, Mutator lines inevitably lose Mu element mobility.The high efficiency of Mu mutagenesis has been exploited in several reverse genetics strategies. The first protocol described used PCR to screen plant DNA samples to find Mu insertions into specific genes using one primer reading out from the conserved Mu terminal inverted repeats (TIRs) and a gene-specific primer [14-17]. Alternatively, survey se
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