Combining automated processing and customized analysis for large-scale sequencing data

Extensive application of high-throughput methods in life sciences has brought substantial new challenges for data analysis. Often many different steps have to be applied to a large number of samples. Here, workflow management systems support scientists through the automated execution of corresponding large analysis workflows. The first part of this cumulative dissertation concentrates on the development of Watchdog, a novel workflow management system for the automated analysis of large-scale experimental data. Watchdog`s main features include straightforward processing of replicate data, support for distributed computer systems, customizable error detection and manual intervention into workflow execution. A graphical user interface enables workflow construction using a pre-defined toolset without programming experience and a community sharing platform allows scientists to share toolsets and workflows efficiently. Furthermore, we implemented methods for resuming execution of interrupted or partially modified workflows and for automated deployment of software using package managers and container virtualization. Using Watchdog, we implemented default analysis workflows for typical types of large-scale biological experiments, such as RNA-seq and ChIP-seq. Although they can be easily applied to new datasets of the same type, at some point such standard workflows reach their limit and customized methods are required to resolve specific questions. Hence, the second part of this dissertation focuses on combining standard analysis workflows with the development of application-specific novel bioinformatics approaches to address questions of interest to our biological collaboration partners. The first study concentrates on identifying the binding motif of the ZNF768 transcription factor, which consists of two anchor regions connected by a variable linker region. As standard motif finding methods detected only the anchors of the motifs separately, a custom method was developed for determining the spaced motif with the linker region. The second study focused on the effect of CDK12 inhibition on transcription. Results obtained from standard RNA-seq analysis indicated substantial transcript shortening upon CDK12 inhibition. We thus developed a new measure to quantify the degree of transcript shortening. In addition, a customized meta-gene analysis framework was developed to model RNA polymerase II progression using ChIP-seq data. This revealed that CDK12 inhibition causes an RNA polymerase II processivity defect resulting in the detected transcript shortening. In summary, the methods developed in this thesis represent both general contributions to large-scale sequencing data analysis and served to resolve specific questions regarding transcription factor binding and regulation of elongating RNA Polymerase II

Influence of niche characteristics and forest type on fern species richness, abundance and plant size along an elevational gradient in Costa Rica

An analysis of the fern vegetation on 156 plots along an elevational gradient (45-3400m) in undisturbed forests in Costa Rica, Central America, showed a hump-shaped pattern of species richness with a maximum of up to 68 species per 400m² at mid-elevations. This study documents the contribution of specific habitats (forest types: ridges, ravines) and niches within them (dead wood, rocks, growth zones in trees) to the local fern richness and the relation of species richness to elevation and climatic variables. Forests along ravines showed significantly higher species richness, presumably caused by high environmental humidity. The mean number of individuals of occupied niches per species increased significantly with elevation, suggesting that the niche breadth of species increased and that the differentiation of niches decreased with elevation. Both findings may explain the reduced fern species richness towards and above the upper treeline, but not at low elevations. The key factors for the decreases of species richness at the extremes of the gradient are likely to involve climatic condition

Decomposing the German East-West wage gap

We demonstrate that almost one half of the observed wage gap between East and WestGermany reflects differences in worker, establishment, and regional characteristicsrather than differences in productivity at the establishment level. Regional price andestablishment size differentials alone account for one quarter of the overall East-Westwage gap. Differences in employees’ characteristics and in productivity deliver muchsmaller but still statistically significant contributions. We derive these results from anOaxaca-Blinder decomposition using unusually rich linked employer-employee data.Our findings are quite stable over the period from 1996 to 2010 and over the wagedistribution

Decomposing the German East-West wage gap

We demonstrate that almost one half of the observed wage gap between East and West Germany reflects differences in worker, establishment, and regional characteristics rather than differences in productivity at the establishment level. Regional price and establishment size differentials alone account for one quarter of the overall East-West wage gap. Differences in employees? characteristics and in productivity deliver much smaller but still statistically significant contributions. We derive these results from an Oaxaca-Blinder decomposition using unusually rich linked employer-employee data. Our findings are quite stable over the period from 1996 to 2010 and over the wage distribution

Russia's Arctic strategy through 2035: grand plans and pragmatic constraints

Russia has adopted a development strategy for the Arctic for the period from October 2020 to 2035. Reflecting hopes and perceived threats associated with the successive warm­ing of the Arctic, it aims to advance development of the region's abundant re­sources, first and foremost oil and gas, and improve living conditions for the popu­lation. In the longer term, the Kremlin hopes to establish the Northern Sea Route as a new global shipping artery. Moscow also worries that an increasingly ice-free Arctic could create new territorial vulnerabilities in its Far North, and is responding by re­building its military presence there. Finally, Moscow also wants to preserve the region's ecological balance. The indications are, however, that the interests of the energy sec­tor and the military will be served, while funding to improve environmental protections and living conditions will remain inadequate. (author's abstract

A Systematic Approach to Constructing Incremental Topology Control Algorithms Using Graph Transformation

Communication networks form the backbone of our society. Topology control algorithms optimize the topology of such communication networks. Due to the importance of communication networks, a topology control algorithm should guarantee certain required consistency properties (e.g., connectivity of the topology), while achieving desired optimization properties (e.g., a bounded number of neighbors). Real-world topologies are dynamic (e.g., because nodes join, leave, or move within the network), which requires topology control algorithms to operate in an incremental way, i.e., based on the recently introduced modifications of a topology. Visual programming and specification languages are a proven means for specifying the structure as well as consistency and optimization properties of topologies. In this paper, we present a novel methodology, based on a visual graph transformation and graph constraint language, for developing incremental topology control algorithms that are guaranteed to fulfill a set of specified consistency and optimization constraints. More specifically, we model the possible modifications of a topology control algorithm and the environment using graph transformation rules, and we describe consistency and optimization properties using graph constraints. On this basis, we apply and extend a well-known constructive approach to derive refined graph transformation rules that preserve these graph constraints. We apply our methodology to re-engineer an established topology control algorithm, kTC, and evaluate it in a network simulation study to show the practical applicability of our approachComment: This document corresponds to the accepted manuscript of the referenced journal articl

A Systematic Approach to Constructing Families of Incremental Topology Control Algorithms Using Graph Transformation

In the communication systems domain, constructing and maintaining network topologies via topology control (TC) algorithms is an important cross-cutting research area. Network topologies are usually modeled using attributed graphs whose nodes and edges represent the network nodes and their interconnecting links. A key requirement of TC algorithms is to fulfill certain consistency and optimization properties to ensure a high quality of service. Still, few attempts have been made to constructively integrate these properties into the development process of TC algorithms. Furthermore, even though many TC algorithms share substantial parts (such as structural patterns or tie-breaking strategies), few works constructively leverage these commonalities and differences of TC algorithms systematically. In previous work, we addressed the constructive integration of consistency properties into the development process. We outlined a constructive, model-driven methodology for designing individual TC algorithms. Valid and high-quality topologies are characterized using declarative graph constraints; TC algorithms are specified using programmed graph transformation. We applied a well-known static analysis technique to refine a given TC algorithm in a way that the resulting algorithm preserves the specified graph constraints. In this paper, we extend our constructive methodology by generalizing it to support the specification of families of TC algorithms. To show the feasibility of our approach, we reneging six existing TC algorithms and develop e-kTC, a novel energy-efficient variant of the TC algorithm kTC. Finally, we evaluate a subset of the specified TC algorithms using a new tool integration of the graph transformation tool eMoflon and the Simonstrator network simulation framework.Comment: Corresponds to the accepted manuscrip

Tests of Full Scale Brick Veneer Steel Stud Walls to Determine Strength and Rain Penetration Characteristics

The design, construction and physical testing of five full scale (2.75 m x 5.2 m) brick veneer rain screen wall specimens are reported. Also, the documentation of the design and fabrication of a new test apparatus and of the development of test procedures are major components of the report. The test program included sequences of air pressure loading stages both with and without simulated rain to establish both the structural and rain penetration performances of the test walls. The test walls included four brick veneer/steel stud specimens and one brick veneer/concrete block specimen. Additional tests were performed on bricks, mortar and masonry assemblages to define relevant characteristics. The design and construction of the wall specimens were consistent with current practices in order to assess the appropriateness of these practices. The major points addressed in the report relate to the vulnerabilities of the wall system to excessive rain penetration and resulting moisture damage. In line with these concerns, the likelihood of veneer cracking, the impact of cracking on structural behaviour and on rain penetration and the importance of cavity compartmentalization were addressed. The conclusions indicated that brick veneer rain screen walls are vulnerable to rain penetration if adequate air tightness in the backup and clean comparted cavities are not provided. Also, it was concluded that veneer cracking is likely under full design loads. It is recommended that the design should address the properties of the brick veneer/backup wall system and that the veneer deflections should be limited to control the size of cracks