Modelling and Quantification of scRNA-seq Experiments and the Transcriptome Dynamics of the Cell Cycle

In dieser Dissertation modellieren und analysieren wir scRNA-Seq-Daten, um Mechanismen, die biologischen Prozessen zugrunde liegen, zu verstehen In scRNA-Seq-Experimenten wird biologisches Rauschen mit technischem Rauschen vermischt. Mittels eines vereinfachten scRNA-Seq-Modells leiten wir eine analytische Verteilungsfunktion für die beobachtete Verteilung unter Kenntnis einer Ausgangsverteilung her. Charakteristiken und sogar ein allgemeines Moment der Ausgangsverteilung können aus der beobachteten Verteilung berechnet werden. Unsere Formeln stellen den Ausgangspunkt zur Quantifizierung von Zellvariabilität dar. Wir haben eine vollständig lineare Analyse von Transkriptomdaten entwickelt, die zeigt, dass sich Zellen während des Zellzyklus auf einer ebenen zirkulären Trajektorie im Transkriptomraum bewegen. In immortalisierten Zelllinien stellen wir fest, dass die Transkriptomdynamiken des Zellzyklus hauptsächlich unabhängig von den Dynamiken anderer Zellprozesse stattfinden. Unser Algorithmus (“Revelio”) bringt eine einfache Methode mit sich, um unsynchronisierte Zellen nach der Zeit zu ordnen und ermöglicht das exakte Entfernen von Zellzykluseffekten. Die Form der Zellzyklus-Trajektorie zeigt, dass der Zellzyklus sich dazu entwickelt hat, Änderungen der transkriptionellen Aktivitäten und der damit verbundenen regulativen Anstrengungen zu minimieren. Dieses Konstruktionsprinzip könnte auch für andere Prozesse relevant sein. Durch die Verwendung von metabolischer Molekülmarkierung erweitern wir Modelle zur mRNA-Kinetik, um dynamische mRNA-Ratenparameter für Transkription, Splicing und Degradation zu erhalten und die Lösungen auf den Zellzyklus anzuwenden. Wir zeigen, dass unser Modell zwischen Genen mit ähnlicher Genexpression aber unterschiedlicher Genregulation unterscheiden kann. Zwar enthalten scRNA-Seq-Daten aktuell noch zu viel technisches Rauschen, unser Modell wird jedoch für das zukünftige Errechnen von dynamischen mRNA-Ratenparametern von großem Nutzen sein.In this dissertation, we model and analyse scRNA-seq data to understand mechanisms underlying biological processes. In scRNA-seq experiments, biological noise gets convoluted with various sources of technical noise. With the help of a simplified scRNA-seq model, we derive an analytical probability distribution function for the observed output distribution given a true input distribution. We find that characteristics and even general moments of the input distribution can be calculated from the output distribution. Our formulas are a starting point for the quantification of cell-to-cell variability. We developed a fully linear analysis of transcriptome data which reveals that cells move along a planar circular trajectory in transcriptome space during the cell cycle. Additionally, we find in immortalized cell lines that cell cycle transcriptome dynamics occur largely independently from other cellular processes. Our algorithm (“Revelio”) offers a simple method to order unsynchronized cells in time and enables the precise removal of cell cycle effects from the data. The shape of the cell cycle trajectory indicates that the cell cycle has evolved to minimize changes of transcriptional activity and their related regulatory efforts. This design principle may be of relevance to other cellular processes. By considering metabolic labelling, we extend existing mRNA kinetic models to obtain dynamic mRNA rate parameters for transcription, splicing and degradation and apply our solutions to the cell cycle. We can distinguish genes with similar expression values but different gene regulation strategies. While current scRNA-seq data contains too much technical noise, the model will be of great value for inferring dynamic mRNA rate parameters in future research

A Functional Model For Information Exploration Systems

Information exploration tasks are inherently complex, ill-structured, and involve sequences of actions usually spread over many sessions. When exploring a dataset, users tend to experiment higher degrees of uncertainty, mostly raised by knowledge gaps concerning the information sources, the task, and the efficiency of the chosen exploration actions, strategies, and tools in supporting the task solution process. Provided these concerns, exploration tools should be designed with the goal of leveraging the mapping between user's cognitive actions and solution strategies onto the current systems' operations. However, state-of-the-art systems fail in providing an expressive set of operations that covers a wide range of exploration problems. There is not a common understanding of neither which operators are required nor in which ways they can be used by explorers. In order to mitigate these shortcomings, this work presents a formal framework of exploration operations expressive enough to describe at least the majority of state-of-the-art exploration interfaces and tasks. We also show how the framework leveraged a new evaluation approach, where we draw precise comparisons between tools concerning the range of exploration tasks they support.Comment: 27 page

Competition between Kondo screening and indirect magnetic exchange in a quantum box

Nanoscale systems of metal atoms antiferromagnetically exchange coupled to several magnetic impurities are shown to exhibit an unconventional re-entrant competition between Kondo screening and indirect magnetic exchange interaction. Depending on the atomic positions of the magnetic moments, the total ground-state spin deviates from predictions of standard Ruderman-Kittel-Kasuya-Yosida perturbation theory. The effect shows up on an energy scale larger than the level width induced by the coupling to the environment and is experimentally verifiable by studying magnetic field dependencies.Comment: 5 pages, 2 figures, v3 with minor change

Entwurf, Konstruktion und Berechnung einer eingleisigen Eisenbahnbrücke als Netzwerkbogenbrücke in Stahlbauweise

In dieser Arbeit wurde eine 110 m weit spannende Netzwerkbogenbrücke für eingleisigen Eisenbahnverkehr unter Lastmodell (LM) 71, auf Basis der Forschungsergebnisse Teichs entworfen und nach den Vorgaben der DIN EN 1990, 1991 und 1993 bemessen. Im Rahmen des Entwurfs wurde eine Variantenuntersuchung durchgeführt. Ferner wurde ein Montagekonzept erstellt

Use of Hypermedia Tools for End-User Development

Software development tools aimed at end-users tend to employ various forms of visual programming because these users find textual programming very difficult to learn. However, visual programming has known scalability issues. As an alternative, we propose hypertextual programming; a technique that represents the program as hypertext and allows the user to both browse it and manipulate it mainly by using navigation. This technique leverages the users' ability to navigate in hyperspace, a widely available skill, to edit the program under development. In order to reap the benefits of this technique, adequate hypertextual editors must be built. Many of the lessons learned in the web engineering area can be used to deal with this problem. This paper discusses the state of the current research efforts behind this novel programming technique.Publicado en Lecture Notes in Computer Science book series (LNCS, vol. 6385).Laboratorio de Investigación y Formación en Informática Avanzad