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Quantum Ordered Binary Decision Diagrams with Repeated Tests
Matthias Homeister,Stephan Waack
Physics , 2005,
Abstract: Quantum branching programs (quantum binary decision diagrams, respectively) are a convenient tool for examining quantum computations using only a logarithmic amount of space. Recently several types of restricted quantum branching programs have been considered, e. g. read--once quantum branching programs. This paper considers quantum ordered binary decision diagrams (QOBDDs) and answers the question: How does the computational power of QOBDDs increase, if we allow repeated tests. Additionally it is described how to synthesize QOBDDs according to Boolean operations.
P-value based visualization of codon usage data
Peter Meinicke, Thomas Brodag, Wolfgang Fricke, Stephan Waack
Algorithms for Molecular Biology , 2006, DOI: 10.1186/1748-7188-1-10
Abstract: The standard genetic code of protein coding DNA sequences shows a redundancy, since different triplet codons may be used to code for the same amino acid. In general, codon usages show organism-specific patterns. However, codon usage variation within a single genome can be an important source of information about gene expression levels and events of horizontal gene transfer. In particular, dimensionality reduction methods have widely been used for the analysis of codon usage patterns in microbial genomes. These methods provide a low-dimensional point representation of genes, where the proximity of gene-specific points indicates a similar codon usage of the associated genes. Hence, the resulting two-dimensional scatter plots enable a total view on the genome which may reveal a clustering of genes according to groups of nearby points. These clusters can for instance provide evidence for horizontal gene transfer according to groups of putative alien genes [1,2] or for translational selection according to groups of highly expressed genes [3,4].As a standard method for scatter plot visualization of codon usage data, researchers mostly resort to the so-called correspondence analysis (CA) which has originally been developed for the analysis of contingency tables [5]. From the original formulation it is not completely clear how CA applies to codon counts. Because different preprocessing and normalization schemes have been proposed, the use of CA in codon usage studies has not been without controversy [6]. Nevertheless, CA has been applied for the analysis of many bacterial genomes, including those of Escherichia coli [1,3], Bacillus subtilis [4,7,8], Borrelia burgdorferi [9,10], Chlamydia trachomatis [11], Mycoplasma genitalium [12], Helicobacter pylori [13] and Pseudomonas aeruginosa [14].Recently, self-organizing maps [15] have been proposed as an alternative visualization method for codon usage data [2,16,17]. Although this method provides a simultaneous clustering of the
Gene prediction in eukaryotes with a generalized hidden Markov model that uses hints from external sources
Mario Stanke, Oliver Sch?ffmann, Burkhard Morgenstern, Stephan Waack
BMC Bioinformatics , 2006, DOI: 10.1186/1471-2105-7-62
Abstract: We present a fairly general method for integration of external information. Our method is based on the evaluation of hints to potentially protein-coding regions by means of a Generalized Hidden Markov Model (GHMM) that takes both intrinsic and extrinsic information into account. We used this method to extend the ab initio gene prediction program AUGUSTUS to a versatile tool that we call AUGUSTUS+. In this study, we focus on hints derived from matches to an EST or protein database, but our approach can be used to include arbitrary user-defined hints. Our method is only moderately effected by the length of a database match. Further, it exploits the information that can be derived from the absence of such matches. As a special case, AUGUSTUS+ can predict genes under user-defined constraints, e.g. if the positions of certain exons are known. With hints from EST and protein databases, our new approach was able to predict 89% of the exons in human chromosome 22 correctly.Sensitive probabilistic modeling of extrinsic evidence such as sequence database matches can increase gene prediction accuracy. When a match of a sequence interval to an EST or protein sequence is used it should be treated as compound information rather than as information about individual positions.Finding protein-coding genes in eukaryotic genomic sequences with in-silico methods remains an important challenge in computational genomics, despite many years of intensive research work. Existing methods fall into two groups with respect to the data they utilize. The first group consists of ab initio programs which use only the query genomic sequence as input. Examples are the programs GENSCAN [1], AUGUSTUS [2] and HMMGene [3] which are HMM-based and GENEID [4]. The second group of gene-finding methods, extrinsic methods, comprises all programs which use data other than the query genomic sequence. Some extrinsic methods use genomic sequences from other species. A cross-species comparison of genomic sequences
Scipio: Using protein sequences to determine the precise exon/intron structures of genes and their orthologs in closely related species
Oliver Keller, Florian Odronitz, Mario Stanke, Martin Kollmar, Stephan Waack
BMC Bioinformatics , 2008, DOI: 10.1186/1471-2105-9-278
Abstract: Scipio is a tool based on the alignment program BLAT to determine the precise gene structure given a protein sequence and a genome sequence. It identifies intron-exon borders and splice sites and is able to cope with sequencing errors and genes spanning several contigs in genomes that have not yet been assembled to supercontigs or chromosomes. Instead of producing a set of hits with varying confidence, Scipio gives the user a coherent summary of locations on the genome that code for the query protein. The output contains information about discrepancies that may result from sequencing errors. Scipio has also successfully been used to find homologous genes in closely related species. Scipio was tested with 979 protein queries against 16 arthropod genomes (intra species search). For cross-species annotation, Scipio was used to annotate 40 genes from Homo sapiens in the primates Pongo pygmaeus abelii and Callithrix jacchus. The prediction quality of Scipio was tested in a comparative study against that of BLAT and the well established program Exonerate.Scipio is able to precisely map a protein query onto a genome. Even in cases when there are many sequencing errors, or when incomplete genome assemblies lead to hits that stretch across multiple target sequences, it very often provides the user with the correct determination of intron-exon borders and splice sites, showing an improved prediction accuracy compared to BLAT and Exonerate. Apart from being able to find genes in the genome that encode the query protein, Scipio can also be used to annotate genes in closely related species.In the post-genome era, sequence data is the entry point for many studies. Often, it is essential to obtain the correct genomic DNA sequences of eukaryotic genes because of the information contained in non-coding regions. For example, the intron regions contain important sites for the regulation of gene transcription, like enhancers, repressors, and silencers [1]. Transcription initiator seque
WebScipio: An online tool for the determination of gene structures using protein sequences
Florian Odronitz, Holger Pillmann, Oliver Keller, Stephan Waack, Martin Kollmar
BMC Genomics , 2008, DOI: 10.1186/1471-2164-9-422
Abstract: WebScipio, a web interface to the Scipio software, allows a user to obtain the corresponding coding sequence structure of a here given a query protein sequence that belongs to an already assembled eukaryotic genome. The resulting gene structure is presented in various human readable formats like a schematic representation, and a detailed alignment of the query and the target sequence highlighting any discrepancies. WebScipio can also be used to identify and characterise the gene structures of homologs in related organisms. In addition, it offers a web service for integration with other programs.WebScipio is a tool that allows users to get a high-quality gene structure prediction from a protein query. It offers more than 250 eukaryotic genomes that can be searched and produces predictions that are close to what can be achieved by manual annotation, for in-species and cross-species searches alike. WebScipio is freely accessible at http://www.webscipio.org webcite.Gene prediction is one of the most important steps in analyzing genome sequences. Mostly, de novo gene prediction is based on sophisticated algorithms that model open reading frames, consensus splice sites, and start and stop codon sequences. Often additional data like EST (Expressed Sequence Tag) sequences or information from cross-species multiple sequence alignments are used. Cross-species DNA sequence comparisons are increasingly being used to identify both coding regions and functional DNA elements [1,2]. These functional elements might be promoter sequences, transcription factor binding sites, termination signals or other regulatory elements. Comparisons of sequences of multiple species have either been performed at a genomic level (e.g. [3,4]) or at the single gene and gene family scale (e.g. [5]).One important aim of most of the large-scale comparative studies has been to improve the annotation of the genomes, like the identification of new genes [6] or new constitutive and alternative exons [7]. Thes
ara Mo ilor – a Regional Term between Economic and Ecological Interests. Some Explorations in the Romanian Periphery
Romanian Review of Regional Studies , 2005,
Abstract: The term “ ara Mo ilor” is very frequently used in the context of the planned gold mining project in Ro ia Montan . The term is as well used in an economic and ecologic way and it is used by those who support the project as well as by its critics. There are a lot of articles in Romanian newspapers and brochures of the last three years combining the gold mining project and the ara Mo ilor topic. It will be analyzed in what different contexts the geographical term is used and the spatial image of ara Mo ilor that is produced in the respective context. Starting with a look into the history of instrumentality of the region it is obvious that there exists a long tradition in using this term for a strong mentality of people who defend their freedom. In an actual context the every day communication of the local population is reproducing this stereotype. The results of a questionnaire shows that the stereotypes used by developer and opponents of the gold mining project met with a strong response. By this way the production and reproduction of a spatial image called “ ara Mo ilor“ can be used successfully for the interests of the actors of both sides. But there exists a geographical differentiation on a small scale between mining and silvicultural areas. This paper focuses on the term “ ara Mo ilor” which is very frequently used when reference is made to the planned gold mining project in Ro ia Montan . The term is also used in economic and ecologic studies and it is used by those who support the project as well as by its critics. There are many articles in Romanian newspapers and brochures of the last three years, which tackle both the gold mining project and the ara Mo ilor topic. Journalists and the public seem to be interested in this matter. I have relied on those arguments which are against the project, as pointed out in Formula AS and on a brochure published in 2002 with the sponsorship of the gold mining company involved in the project. We shall analyze the different contexts where the geographical term is used and the spatial image of ara Mo ilor produced in the respective context.
Cross-species protein sequence and gene structure prediction with fine-tuned Webscipio 2.0 and Scipio
Klas Hatje, Oliver Keller, Bj?rn Hammesfahr, Holger Pillmann, Stephan Waack, Martin Kollmar
BMC Research Notes , 2011, DOI: 10.1186/1756-0500-4-265
Abstract: Scipio and WebScipio have fundamentally been extended to better reconstruct very short exons and intron splice sites and to be better suited for cross-species gene structure predictions. The Needleman-Wunsch algorithm has been implemented for the search for short parts of the query sequence that were not recognized by Blat. Those regions might either be short exons, divergent sequence at intron splice sites, or very divergent exons. We have shown the benefit and use of new parameters with several protein examples from completely different protein families in searches against species from several kingdoms of the eukaryotes. The performance of the new Scipio version has been tested in comparison with several similar tools.With the new version of Scipio very short exons, terminal and internal, of even just one amino acid can correctly be reconstructed. Scipio is also able to correctly predict almost all genes in cross-species searches even if the ancestors of the species separated more than 100 Myr ago and if the protein sequence identity is below 80%. For our test cases Scipio outperforms all other software tested. WebScipio has been restructured and provides easy access to the genome assemblies of about 640 eukaryotic species. Scipio and WebScipio are freely accessible at http://www.webscipio.org webcite.Whole genome sequences of eukaryotes are generated with increasing speed [1]. While the focus at the beginning of high-throughput DNA sequencing was on model organisms and the human genome, for which tremendous amounts of secondary data was available, the aims have shifted to organisms of medical or economic relevance (e.g. Plasmodium falciparum [2] or Phytophthora ramorum [3]), to the comparative analysis of entire taxa (e.g. the Drosophila clade [4] or Candida species [5]), and, very recently, to organisms of evolutionary interest (e.g. Trichoplax adhaerens [6] or Volvox carteri [7]). However, gene catalogues are only available for a small part of the sequenced org
Coupled mutation finder: A new entropy-based method quantifying phylogenetic noise for the detection of compensatory mutations
Gültas Mehmet,Haubrock Martin,Tüysüz Nesrin,Waack Stephan
BMC Bioinformatics , 2012, DOI: 10.1186/1471-2105-13-225
Abstract: Background The detection of significant compensatory mutation signals in multiple sequence alignments (MSAs) is often complicated by noise. A challenging problem in bioinformatics is remains the separation of significant signals between two or more non-conserved residue sites from the phylogenetic noise and unrelated pair signals. Determination of these non-conserved residue sites is as important as the recognition of strictly conserved positions for understanding of the structural basis of protein functions and identification of functionally important residue regions. In this study, we developed a new method, the Coupled Mutation Finder (CMF) quantifying the phylogenetic noise for the detection of compensatory mutations. Results To demonstrate the effectiveness of this method, we analyzed essential sites of two human proteins: epidermal growth factor receptor (EGFR) and glucokinase (GCK). Our results suggest that the CMF is able to separate significant compensatory mutation signals from the phylogenetic noise and unrelated pair signals. The vast majority of compensatory mutation sites found by the CMF are related to essential sites of both proteins and they are likely to affect protein stability or functionality. Conclusions The CMF is a new method, which includes an MSA-specific statistical model based on multiple testing procedures that quantify the error made in terms of the false discovery rate and a novel entropy-based metric to upscale BLOSUM62 dissimilar compensatory mutations. Therefore, it is a helpful tool to predict and investigate compensatory mutation sites of structural or functional importance in proteins. We suggest that the CMF could be used as a novel automated function prediction tool that is required for a better understanding of the structural basis of proteins. The CMF server is freely accessible at http://cmf.bioinf.med.uni-goettingen.de.
Score-based prediction of genomic islands in prokaryotic genomes using hidden Markov models
Stephan Waack, Oliver Keller, Roman Asper, Thomas Brodag, Carsten Damm, Wolfgang Fricke, Katharina Surovcik, Peter Meinicke, Rainer Merkl
BMC Bioinformatics , 2006, DOI: 10.1186/1471-2105-7-142
Abstract: We have implemented the program SIGI-HMM that predicts GIs and the putative donor of each individual alien gene. It is based on the analysis of codon usage (CU) of each individual gene of a genome under study. CU of each gene is compared against a carefully selected set of CU tables representing microbial donors or highly expressed genes. Multiple tests are used to identify putatively alien genes, to predict putative donors and to mask putatively highly expressed genes. Thus, we determine the states and emission probabilities of an inhomogeneous hidden Markov model working on gene level. For the transition probabilities, we draw upon classical test theory with the intention of integrating a sensitivity controller in a consistent manner. SIGI-HMM was written in JAVA and is publicly available. It accepts as input any file created according to the EMBL-format.It generates output in the common GFF format readable for genome browsers. Benchmark tests showed that the output of SIGI-HMM is in agreement with known findings. Its predictions were both consistent with annotated GIs and with predictions generated by different methods.SIGI-HMM is a sensitive tool for the identification of GIs in microbial genomes. It allows to interactively analyze genomes in detail and to generate or to test hypotheses about the origin of acquired genes.Horizontal gene transfer (HGT) is a process that results in the acquisition of novel genes originating from perhaps taxonomically unrelated species. This phenomenon is frequent among microbes and is considered a means of rapid adaptation to changing environmental demands [1]. Pieces of DNA acquired via HGT frequently have a considerable length. These patches have been called genomic islands (GI) or due to their role and more specifically pathogenicity islands [2] or symbiotic islands [3].Several methods have been developed for the prediction of GIs based on different approaches to identify putatively alien (pA) genes [4-12]. Each of these concep
Association between Magnetic Resonance Imaging and the Result of Medial Branch Blocks  [PDF]
Stephan Klessinger, Wolfgang Freund
Pain Studies and Treatment (PST) , 2017, DOI: 10.4236/pst.2017.51001
Abstract: The aim of this retrospective practice audit was to assess the correlation between painful zygapophysial joints and changes seen in magnetic resonance imaging (MRI). Patients with unilateral pain were tested with controlled medial branch blocks. The MRI scans of patients with a positive response were compared blinded with normal MRI scans. The dimensions of the joint were assessed and osteoarthritis was graded. Fifteen symptomatic patients and 15 asymptomatic patients were included and evaluated. Comparison of the joints showed that the maximum diameter of symptomatic joints was significantly larger, and the grading of osteoarthritis was significantly higher for symptomatic joints. No healthy patient was assigned a grade 3. Grades 2 and 3 were found significantly more often in symptomatic patients. Only one symptomatic joint was assigned grade 0. Grade 0 was found significantly more often in asympto-matic patients. The presented MRI technique has limited value as a diagnostic test for lumbar zygapophysial joint pain. It is not possible to detect a single symptomatic joint. However, the osteoarthritis grading for the lumbar zyg-apophysial joints might be helpful for finding predictors for negative response if the results of the rating are grade zero. Therefore, unnecessary medial branch blocks might be avoided.
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