@phdthesis{Koenig2005, author = {K{\"o}nig, Stefan}, title = {Ver{\"a}nderung der Beinachse beim Einbau einer CPR-Kniegelenksendoprothese mit alleiniger Ausrichtung nach der Bandspannung}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-13789}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2005}, abstract = {In der vorliegenden Arbeit wurden postoperative Beinachsenaufnahmen nach Implantation einer CPR-Knieprothese begutachtet. Es galt dabei die Frage zu kl{\"a}ren, ob die Ausrichtung des femoralen Implantates allein nach der Kollateralbandspannung ein korrektes Alignment des Beines erm{\"o}glicht. In dieser Arbeit wurde ein Quotient eingef{\"u}hrt, der eine exakte Beschreibung des Traglinienverlaufes im Bereich des Kniegelenkes zul{\"a}sst. Dieser „Plateau-Quotient" korreliert hervorragend mit dem frontalen Kniegelenkswinkel (R=96,9\%), und ist damit ein geeignetes Werkzeug, eine Kniegelenksdeformit{\"a}t zu beschreiben. Der Mittelwert der postoperativen anatomischen Beinachsen entspricht dem in der Literatur und in Lehrb{\"u}chern der Anatomie angegebenen Wert des frontalen Kniewinkels von 175°. Die Streuung der Werte (165°-186°; Standardabweichung 3,96° ) ist ebenfalls vergleichbar. Die postoperativ resultierende Beinachse bei Implantation einer CPR-Knieprothese mit alleiniger Ausrichtung nach der Kollateralbandspannung ist offensichtlich mit der klassischen, anatomischen Resektion anhand eines definierten Valguswinkels vergleichbar. Ob diese Orientierung der Prothesenimplantation nach der Spannung der Kollateralb{\"a}nder auch - wie theoretisch postuliert - klinisch stabilere Kniegelenke als bei Orientierung anhand der Achsenverh{\"a}ltnisse ergibt und ob sich dieser Vorteil in einer Verbesserung der Langzeitergebnisse niederschl{\"a}gt, muss dringend durch weitere Studien untersucht werden.}, language = {de} } @article{MergetKoetschanHackletal.2012, author = {Merget, Benjamin and Koetschan, Christian and Hackl, Thomas and F{\"o}rster, Frank and Dandekar, Thomas and M{\"u}ller, Tobias and Schultz, J{\"o}rg and Wolf, Matthias}, title = {The ITS2 Database}, series = {Journal of Visual Expression}, volume = {61}, journal = {Journal of Visual Expression}, number = {e3806}, doi = {10.3791/3806}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-124600}, year = {2012}, abstract = {The internal transcribed spacer 2 (ITS2) has been used as a phylogenetic marker for more than two decades. As ITS2 research mainly focused on the very variable ITS2 sequence, it confined this marker to low-level phylogenetics only. However, the combination of the ITS2 sequence and its highly conserved secondary structure improves the phylogenetic resolution1 and allows phylogenetic inference at multiple taxonomic ranks, including species delimitation. The ITS2 Database presents an exhaustive dataset of internal transcribed spacer 2 sequences from NCBI GenBank accurately reannotated. Following an annotation by profile Hidden Markov Models (HMMs), the secondary structure of each sequence is predicted. First, it is tested whether a minimum energy based fold (direct fold) results in a correct, four helix conformation. If this is not the case, the structure is predicted by homology modeling. In homology modeling, an already known secondary structure is transferred to another ITS2 sequence, whose secondary structure was not able to fold correctly in a direct fold. The ITS2 Database is not only a database for storage and retrieval of ITS2 sequence-structures. It also provides several tools to process your own ITS2 sequences, including annotation, structural prediction, motif detection and BLAST search on the combined sequence-structure information. Moreover, it integrates trimmed versions of 4SALE and ProfDistS for multiple sequence-structure alignment calculation and Neighbor Joining tree reconstruction. Together they form a coherent analysis pipeline from an initial set of sequences to a phylogeny based on sequence and secondary structure. In a nutshell, this workbench simplifies first phylogenetic analyses to only a few mouse-clicks, while additionally providing tools and data for comprehensive large-scale analyses.}, language = {en} } @article{LindgreenUmuLaietal.2014, author = {Lindgreen, Stinus and Umu, Sinan Uğur and Lai, Alicia Sook-Wei and Eldai, Hisham and Liu, Wenting and McGimpsey, Stephanie and Wheeler, Nicole E. and Biggs, Patrick J. and Thomson, Nick R. and Barquist, Lars and Poole, Anthony M. and Gardner, Paul P.}, title = {Robust Identification of Noncoding RNA from Transcriptomes Requires Phylogenetically-Informed Sampling}, series = {PLOS Computational Biology}, volume = {10}, journal = {PLOS Computational Biology}, number = {10}, doi = {10.1371/journal.pcbi.1003907}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-115259}, pages = {e1003907}, year = {2014}, abstract = {Noncoding RNAs are integral to a wide range of biological processes, including translation, gene regulation, host-pathogen interactions and environmental sensing. While genomics is now a mature field, our capacity to identify noncoding RNA elements in bacterial and archaeal genomes is hampered by the difficulty of de novo identification. The emergence of new technologies for characterizing transcriptome outputs, notably RNA-seq, are improving noncoding RNA identification and expression quantification. However, a major challenge is to robustly distinguish functional outputs from transcriptional noise. To establish whether annotation of existing transcriptome data has effectively captured all functional outputs, we analysed over 400 publicly available RNA-seq datasets spanning 37 different Archaea and Bacteria. Using comparative tools, we identify close to a thousand highly-expressed candidate noncoding RNAs. However, our analyses reveal that capacity to identify noncoding RNA outputs is strongly dependent on phylogenetic sampling. Surprisingly, and in stark contrast to protein-coding genes, the phylogenetic window for effective use of comparative methods is perversely narrow: aggregating public datasets only produced one phylogenetic cluster where these tools could be used to robustly separate unannotated noncoding RNAs from a null hypothesis of transcriptional noise. Our results show that for the full potential of transcriptomics data to be realized, a change in experimental design is paramount: effective transcriptomics requires phylogeny-aware sampling.}, language = {en} } @article{WolfKuonenDandekaretal.2015, author = {Wolf, Beat and Kuonen, Pierre and Dandekar, Thomas and Atlan, David}, title = {DNAseq workflow in a diagnostic context and an example of a user friendly implementation}, series = {BioMed Research International}, journal = {BioMed Research International}, number = {403497}, doi = {10.1155/2015/403497}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-144527}, year = {2015}, abstract = {Over recent years next generation sequencing (NGS) technologies evolved from costly tools used by very few, to a much more accessible and economically viable technology. Through this recently gained popularity, its use-cases expanded from research environments into clinical settings. But the technical know-how and infrastructure required to analyze the data remain an obstacle for a wider adoption of this technology, especially in smaller laboratories. We present GensearchNGS, a commercial DNAseq software suite distributed by Phenosystems SA. The focus of GensearchNGS is the optimal usage of already existing infrastructure, while keeping its use simple. This is achieved through the integration of existing tools in a comprehensive software environment, as well as custom algorithms developed with the restrictions of limited infrastructures in mind. This includes the possibility to connect multiple computers to speed up computing intensive parts of the analysis such as sequence alignments. We present a typical DNAseq workflow for NGS data analysis and the approach GensearchNGS takes to implement it. The presented workflow goes from raw data quality control to the final variant report. This includes features such as gene panels and the integration of online databases, like Ensembl for annotations or Cafe Variome for variant sharing.}, language = {en} } @article{RybalkaWolfAndersenetal.2013, author = {Rybalka, Nataliya and Wolf, Matthias and Andersen, Robert and Friedl, Thomas}, title = {Congruence of chloroplast- and nuclear-encoded DNA sequence variations used to assess species boundaries in the soil microalga Heterococcus (Stramenopiles, Xanthophyceae)}, series = {BMC Evolutionary Biology}, volume = {13}, journal = {BMC Evolutionary Biology}, number = {39}, issn = {1471-2148}, doi = {10.1186/1471-2148-13-39}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-121848}, year = {2013}, abstract = {Background: Heterococcus is a microalgal genus of Xanthophyceae (Stramenopiles) that is common and widespread in soils, especially from cold regions. Species are characterized by extensively branched filaments produced when grown on agarized culture medium. Despite the large number of species described exclusively using light microscopic morphology, the assessment of species diversity is hampered by extensive morphological plasticity. Results: Two independent types of molecular data, the chloroplast-encoded psbA/rbcL spacer complemented by rbcL gene and the internal transcribed spacer 2 of the nuclear rDNA cistron (ITS2), congruently recovered a robust phylogenetic structure. With ITS2 considerable sequence and secondary structure divergence existed among the eight species, but a combined sequence and secondary structure phylogenetic analysis confined to helix II of ITS2 corroborated relationships as inferred from the rbcL gene phylogeny. Intra-genomic divergence of ITS2 sequences was revealed in many strains. The 'monophyletic species concept', appropriate for microalgae without known sexual reproduction, revealed eight different species. Species boundaries established using the molecular-based monophyletic species concept were more conservative than the traditional morphological species concept. Within a species, almost identical chloroplast marker sequences (genotypes) were repeatedly recovered from strains of different origins. At least two species had widespread geographical distributions; however, within a given species, genotypes recovered from Antarctic strains were distinct from those in temperate habitats. Furthermore, the sequence diversity may correspond to adaptation to different types of habitats or climates. Conclusions: We established a method and a reference data base for the unambiguous identification of species of the common soil microalgal genus Heterococcus which uses DNA sequence variation in markers from plastid and nuclear genomes. The molecular data were more reliable and more conservative than morphological data.}, language = {en} } @phdthesis{Rummey2002, author = {Rummey, Christian}, title = {3D-QSAR-Untersuchungen an antimalaria-aktiven Naphthylisochinolin-Alkaloiden}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-4599}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2002}, abstract = {Aufbauend auf einen Datensatz von etwa 70 antimalaria-aktiven Verbindungen wurde mit Hilfe des CoMSIA-Verfahrens ein QSAR(Qantitative Structure Activity Relationship)-Modell erstellt, das in der Lage ist antiplasmodiale Aktivit{\"a}ten von Verbindungen aus der Substanzklasse der Naphthylisochinolin-Alkaloide vorherzusagen. Da die behandelten Strukturen ein sehr kompliziertes konformatives Verhalten aufweisen, mussten f{\"u}r ein m{\"o}glichst flexibles Alignment (unter Verwendung von FLEXS und GASP) eigene Abl{\"a}ufe entwickelt werden, die schließlich weitestgehend automatisiert werden konnten. Das erstellte Modell erlaubte es dar{\"u}ber hinaus, die f{\"u}r die Aktivit{\"a}t verantwortlichen strukturellen Merkmale zu identifizieren und so entscheidende Anregungen zur Vereinfachung des relativ komplizierten Grundger{\"u}sts zu geben. Die Vorschl{\"a}ge wurden zu einem großen Teil bereits synthetisch verwirklicht, wobei die anschließend experimentell gefundenen Aktivit{\"a}ten die vorher berechneten sehr gut best{\"a}tigten. Die neu entwickelten Substanzen befinden sich derzeit im Patentpr{\"u}fungsverfahren.}, subject = {Malaria}, language = {de} }