Focus: A Graph Approach for Data-Mining and Domain-Specific Assembly of Next Generation Sequencing Data

Next Generation Sequencing (NGS) has emerged as a key technology leading to revolutionary breakthroughs in numerous biomedical research areas. These technologies produce millions to billions of short DNA reads that represent a small fraction of the original target DNA sequence. These short reads contain little information individually but are produced at a high coverage of the original sequence such that many reads overlap. Overlap relationships allow for the reads to be linearly ordered and merged by computational programs called assemblers into long stretches of contiguous sequence called contigs that can be used for research applications. Although the assembly of the reads produced by NGS remains a difficult task, it is the process of extracting useful knowledge from these relatively short sequences that has become one of the most exciting and challenging problems in Bioinformatics. The assembly of short reads is an aggregative process where critical information is lost as reads are merged into contigs. In addition, the assembly process is treated as a black box, with generic assembler tools that do not adapt to input data set characteristics. Finally, as NGS data throughput continues to increase, there is an increasing need for smart parallel assembler implementations. In this dissertation, a new assembly approach called Focus is proposed. Unlike previous assemblers, Focus relies on a novel hybrid graph constructed from multiple graphs at different levels of granularity to represent the assembly problem, facilitating information capture and dynamic adjustment to input data set characteristics. This work is composed of four specific aims: 1) The implementation of a robust assembly and analysis tool built on the hybrid graph platform 2) The development and application of graph mining to extract biologically relevant features in NGS data sets 3) The integration of domain specific knowledge to improve the assembly and analysis process. 4) The construction of smart parallel computing approaches, including the application of energy-aware computing for NGS assembly and knowledge integration to improve algorithm performance. In conclusion, this dissertation presents a complete parallel assembler called Focus that is capable of extracting biologically relevant features directly from its hybrid assembly graph

Control of Neuronal Circuit Assembly by Gtpase Regulators

One of the most remarkable features of the central nervous system is the exquisite specificity of its synaptic connections, which is crucial for the functioning of neuronal circuits. Thus, understanding the cellular and molecular mechanisms leading to the precise assembly of neuronal circuits is a major focus of developmental neurobiology. The structural organization and specific connectivity of neuronal circuits arises from a series of morphological transformations: neuronal differentiation, migration, axonal guidance, axonal and dendritic arbor growth and, eventually, synapse formation. Changes in neuronal morphology are driven by cell intrinsic programs and by instructive signals from the environment, which are transduced by transmembrane receptors on the neuronal cell surface. Intracellularly, cytoskeletal rearrangements orchestrate the dynamic modification of neuronal morphology. A central question is how the activation of a neuronal cell surface receptor triggers the intracellular cytoskeletal rearrangements that mediate morphological transformations. A group of proteins linked to the regulation of cytoskeletal dynamics are the small GTPases of the Rho family. Small RhoGTPases are regulated by GTPase exchange factors (GEF) and GTPase activating proteins (GAP), which can switch GTPases into "on or off" states, respectively. It is thought that GEFs and GAPs function as intracellular mediators between transmembrane receptors and RhoGTPases to regulate cytoskeletal rearrangements. During my dissertation I identified the GAP α2-chimaerin as an essential downstream effector of the axon guidance receptor EphA4, in the assembly of neuronal locomotor circuits in the mouse. Furthermore, I identified two novel neuronal GAPs, mSYD-1A and mSYD-1B, which interact with components of the presynaptic active zone and which may contribute to presynaptic assembly downstream of synaptic cell surface receptors

Spatially regularized estimation for the analysis of DCE-MRI data

Competing compartment models of different complexities have been used for the quantitative analysis of Dynamic Contrast-Enhanced Magnetic Resonance Imaging data. We present a spatial Elastic Net approach that allows to estimate the number of compartments for each voxel such that the model complexity is not fixed a priori. A multi-compartment approach is considered, which is translated into a restricted least square model selection problem. This is done by using a set of basis functions for a given set of candidate rate constants. The form of the basis functions is derived from a kinetic model and thus describes the contribution of a specific compartment. Using a spatial Elastic Net estimator, we chose a sparse set of basis functions per voxel, and hence, rate constants of compartments. The spatial penalty takes into account the voxel structure of an image and performs better than a penalty treating voxels independently. The proposed estimation method is evaluated for simulated images and applied to an in-vivo data set

Graph mining for next generation sequencing: leveraging the assembly graph for biological insights

Total genome length estimation for NG50. This spreadsheet file contains the calculation of the average genome lengths for the complete reference sequences available through the NCBI RefSeq database for the most abundant genera in the Crohn’s and healthy data sets. The estimated total genome length is also calculated in this file. (XLSX 21 kb

Regularized estimation and model selection in compartment models

Dynamic imaging series acquired in medical and biological research are often analyzed with the help of compartment models. Compartment models provide a parametric, nonlinear function of interpretable, kinetic parameters describing how some concentration of interest evolves over time. Aiming to estimate the kinetic parameters, this leads to a nonlinear regression problem. In many applications, the number of compartments needed in the model is not known from biological considerations but should be inferred from the data along with the kinetic parameters. As data from medical and biological experiments are often available in the form of images, the spatial data structure of the images has to be taken into account. This thesis addresses the problem of parameter estimation and model selection in compartment models. Besides a penalized maximum likelihood based approach, several Bayesian approaches-including a hierarchical model with Gaussian Markov random field priors and a model state approach with flexible model dimension-are proposed and evaluated to accomplish this task. Existing methods are extended for parameter estimation and model selection in more complex compartment models. However, in nonlinear regression and, in particular, for more complex compartment models, redundancy issues may arise. This thesis analyzes difficulties arising due to redundancy issues and proposes several approaches to alleviate those redundancy issues by regularizing the parameter space. The potential of the proposed estimation and model selection approaches is evaluated in simulation studies as well as for two in vivo imaging applications: a dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) study on breast cancer and a study on the binding behavior of molecules in living cell nuclei observed in a fluorescence recovery after photobleaching (FRAP) experiment

Matchpoint für die Sport-PR?

In der vorliegenden Arbeit geht es um die Analyse und Evaluation von PR-Strategien im Sport, um zu untersuchen, welchen Beitrag diese für den Sport leisten können. Im 21. Jahrhundert hat Social Media Einzug in die Medienlandschaft gehalten und etabliert sich auch immer mehr als neue PR-Strategie. Die vorliegende Arbeit beschäftigt sich mit der PR-Evaluation im Sport und wird konkret am Beispiel des österreichischen Tennisverbands untersucht. Nach Darstellung der verwendeten kommunikationswissenschaftlichen Theorien und PR-Theorien wird näher auf die Evaluationsmodelle und im weiteren Evaluationsmethoden eingegangen, bevor konkret der ÖTV als Untersuchungsgegenstand und seine PR-Strategien vorgestellt werden. Ziel der empirischen Untersuchung ist, den Erfolg von Social Media-Aktivitäten in der Sport-PR und dessen Einfluss auf die klassische PR-Arbeit zu messen. Die Untersuchung erfolgte mittels Methodenmix aus qualitativem Experteninterview und quantitativer Inhaltsanalyse der Facebook-Seite, welche exemplarisch für die Social Media-Aktivitäten des ÖTVs hinsichtlich Qualität und inhaltlicher Relevanz analysiert und anschließend in die Gesamtkommunikation des ÖTVs eingegliedert wird. Zusammengefasst ist das Ziel, im Kontext von kommunikationswissenschaftlichen Theorien, die PR-Strategien vom ÖTV, stellvertretend für die Sport-PR-Branche in Österreich, zu analysieren.The following paper on Analysis and Evaluation of PR-Strategies in Sports aims at determining what contributions they are able to make. In the 21st century, social media entered the media landscape and is gradually being established as a new PR-strategy. The following paper discusses PR-evaluation in Sports, exemplified by the Austrian Tennis Association (ÖTV). After introducing the theories on communicative studies and PR used in this paper, the issue of models and methods of evaluation will be closely addresses before directly discussing the ÖTV and its PR-strategies as the papers main object of investigation. Purpose of the empirical investigation is to measure the success of social media activities used for the PR of sports and its influence on traditional PR. The methods used are a combination of qualitative interviews with experts and quantitative content analysis of the ÖTV’s Facebook-page, which will be analysed as an example for the ÖTV’s social media activities regarding its quality and content relevance and will be incorporated into the ÖTV’s full-scale communication services hereafter. Its goal is to analyse the PR-strategies of the ÖTV in the context of communicative studies, representative for the PR-branch in Austrian sports

Incidents in Educational and Academic Chemistry Laboratories: A Comparative Case Study Project

For this thesis, eleven published case studies of laboratory incidents that involved hazardous chemicals and occurred at primary educational and academic institutions were compared. The important information on the incident settings was used to construct bowtie diagrams. This visual method served as a helpful tool to find similarities and differences of the incidents. Common themes between the different cases were lack of supervision, lack of training, deviation from established procedures, and an inadequate or delayed emergency response. Failing barriers provided several pathways for the incidents to occur. Therefore, hierarchical risk management models could not adequately accommodate dynamic teaching environments. The results of this project show that primary educational and academic facilities need to make improvements to their risk management systems and work operations. Laboratory incidents continue to occur at a high frequency. Therefore, effective methods on how to teach chemical health and safety and how to communicate occupational risk need to be developed

Laser Secondary Neutral Mass Spectrometry und Immunfluoreszenzmikroskopie zur Charakterisierung der Biomineralisation von Monolagen und 3-dimensionalen Osteoblastenkulturen

Die Biomineralisation des Knochens ist ein vielstufiger Prozess, in dem zum einen Collagen-Typ I und verschiedene nicht-collagene Proteine, wie z.B. Bone Sialoprotein und Osteonectin mit Unterstützung der Adhäsionsproteine Actin und Fibronectin eine Matrix bilden, in den zum anderen aber auch Kalzium und weitere anorganische Elemente involviert sind. Ziel dieser in vitro Studie ist die Charakterisierung der Matrixmineralisation anhand der von bovinen Osteoblasten-ähnlichen Zellen synthetisierten Proteine, deren Matrixstrukturen mit Hilfe einer fluoreszenzmikroskopischen Analyse beurteilt werden können. Außerdem werden die Verteilungen der verschiedenen anorganischen Elemente mittels Laser-SNMS (Secondary Neutral Mass Spectrometry) anhand der chemischen Struktur der Zellkultur untersucht. Die mittels SNMS bestimmte Elementverteilung zeigt z.B., dass Kalium vor Beginn der Nukleation angereichert wird