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Background: Computational tools for the investigation of transcriptional regulation, in particular of transcription factor binding sites (TFBS), in evolutionary context are developed. Existing sequence based tools prediction such binding sites do not consider their actual functionality, although it is known that besides the base sequence many other aspects are relevant for binding and for the effects of that binding. In particular in Eukaryotes a perfectly matching sequence motif is neither necessary nor sufficient for a functional transcription factor binding site. Published work in the field of transcriptional regulation frequently focus on the prediction of putative transcription factor binding sites based on sequence similarity to known binding sites. Furthermore, among the related software, only a small number implements visualization of the evolution of transcription factor binding sites or the integration of other regulation related data. The interface of many tools is made for computer scientists, although the actual interpretation of their outcome needs profound biological background knowledge. Results and Discussion: The tool presented in this thesis, "ReXSpecies" is a web application. Therefore, it is ready to use for the end user without installation providing a graphical user interface. Besides extensive automation of analyses of transcriptional regulation (the only necessary input are the genomic coordinates of a regulatory region), new techniques to visualize the evolution of transcription factor binding sites were developed. Furthermore, an interface to genome browsers was implemented to enable scientists to comprehensively analyze their regulatory regions with respect to other regulation relevant data. ReXSpecies contains a novel algorithm that searches for evolutionary conserved patterns of transcription factor binding sites, which could imply functionality. Such patterns were verified using some known transcription factor binding sites of genes involved in pluripotency. In the appendix, efficiency and correctness of the used algorithm are discussed. Furthermore, a novel algorithm to color phylogenetic trees intuitively is presented. In the thesis, new possibilities to render evolutionary conserved sets of transcription factor binding sites are developed. The thesis also discusses the evolutionary conservation of regulation and its context dependency. An important source of errors in the analysis of regulatory regions using comparative genetics is probably to find and to align homologous regulatory regions. Some alternatives to using sequence similarity alone are discussed. Outlook: Other possibilities to find (functional) homologous regulatory regions (besides whole-genome-alignments currently used) are BLAST searches, local alignments, homology databases and alignment-free approaches. Using one ore more of these alternatives could reduce the number of artifacts by reduction of the number of regions that are erroneously declared homologous. To achieve more robust predictions of transcription, the author suggests to use other regulation related data besides sequence data only. Therefore, the use and extension of existing tools, in particular of systems biology, is proposed.
Data quality assessments (DQA) are necessary to ensure valid research results. Despite the growing availability of tools of relevance for DQA in the R language, a systematic comparison of their functionalities is missing. Therefore, we review R packages related to data quality (DQ) and assess their scope against a DQ framework for observational health studies. Based on a systematic search, we screened more than 140 R packages related to DQA in the Comprehensive R Archive Network. From these, we selected packages which target at least three of the four DQ dimensions (integrity, completeness, consistency, accuracy) in a reference framework. We evaluated the resulting 27 packages for general features (e.g., usability, metadata handling, output types, descriptive statistics) and the possible assessment’s breadth. To facilitate comparisons, we applied all packages to a publicly available dataset from a cohort study. We found that the packages’ scope varies considerably regarding functionalities and usability. Only three packages follow a DQ concept, and some offer an extensive rule-based issue analysis. However, the reference framework does not include a few implemented functionalities, and it should be broadened accordingly. Improved use of metadata to empower DQA and user-friendliness enhancement, such as GUIs and reports that grade the severity of DQ issues, stand out as the main directions for future developments.