Synthesizing species trees from gene trees using the parameterized and graph-theoretic approaches

Gene trees describe how parts of the species have evolved over time, and it is assumed that gene trees have evolved along the branches of the species tree. However, some of gene trees are often discordant with the corresponding species tree due to the complicated evolution history of genes. To overcome this obstacle, median problems have emerged as a major tool for synthesizing species trees by reconciling discordance in a given collection of gene trees. Given a collection of gene trees and a cost function, the median problem seeks a tree, called median tree, that minimizes the overall cost to the gene trees. Median tree problems are typically NP-hard, and there is an increased interest in making such median tree problems available for large-scale species tree construction. In this thesis work, we first show that the gene duplication median tree problem satisfied the weaker version of the Pareto property and propose a parameterized algorithm to solve the gene duplication median tree problem. Second, we design two efficient methods to handle the issues of applying the parameterized algorithm to unrooted gene trees which are sampled from the different species. Third, we introduce the graph-theoretic formulation of the Robinson-Foulds median tree problem and a new tree edit operation. Fourth, we propose a new metric between two phylogenetic trees and examine the statistical properties of the metric. Finally, we propose a new clustering criteria in a bipartite network and propose a new NP-hard problem and its ILP formulation

Interoperability of Traffic Infrastructure Planning and Geospatial Information Systems

Building Information Modelling (BIM) as a Model-based design facilitates to investigate multiple solutions in the infrastructure planning process. The most important reason for implementing model-based design is to help designers and to increase communication between different design parties. It decentralizes and coordinates team collaboration and facilitates faster and lossless project data exchange and management across extended teams and external partners in project lifecycle. Infrastructure are fundamental facilities, services, and installations needed for the functioning of a community or society, such as transportation, roads, communication systems, water and power networks, as well as power plants. Geospatial Information Systems (GIS) as the digital representation of the world are systems for maintaining, managing, modelling, analyzing, and visualizing of the world data including infrastructure. High level infrastructure suits mostly facilitate to analyze the infrastructure design based on the international or user defined standards. Called regulation1-based design, this minimizes errors, reduces costly design conflicts, increases time savings and provides consistent project quality, yet mostly in standalone solutions. Tasks of infrastructure usually require both model based and regulation based design packages. Infrastructure tasks deal with cross-domain information. However, the corresponding data is split in several domain models. Besides infrastructure projects demand a lot of decision makings on governmental as well as on private level considering different data models. Therefore lossless flow of project data as well as documents like regulations across project team, stakeholders, governmental and private level is highly important. Yet infrastructure projects have largely been absent from product modelling discourses for a long time. Thus, as will be explained in chapter 2 interoperability is needed in infrastructure processes. Multimodel (MM) is one of the interoperability methods which enable heterogeneous data models from various domains get bundled together into a container keeping their original format. Existing interoperability methods including existing MM solutions can’t satisfactorily fulfill the typical demands of infrastructure information processes like dynamic data resources and a huge amount of inter model relations. Therefore chapter 3 concept of infrastructure information modelling investigates a method for loose and rule based coupling of exchangeable heterogeneous information spaces. This hypothesis is an extension for the existing MM to a rule-based Multimodel named extended Multimodel (eMM) with semantic rules – instead of static links. The semantic rules will be used to describe relations between data elements of various models dynamically in a link-database. Most of the confusion about geospatial data models arises from their diversity. In some of these data models spatial IDs are the basic identities of entities and in some other data models there are no IDs. That is why in the geospatial data, data structure is more important than data models. There are always spatial indexes that enable accessing to the geodata. The most important unification of data models involved in infrastructure projects is the spatiality. Explained in chapter 4 the method of infrastructure information modelling for interoperation in spatial domains generate interlinks through spatial identity of entities. Match finding through spatial links enables any kind of data models sharing spatial property get interlinked. Through such spatial links each entity receives the spatial information from other data models which is related to the target entity due to sharing equivalent spatial index. This information will be the virtual properties for the object. The thesis uses Nearest Neighborhood algorithm for spatial match finding and performs filtering and refining approaches. For the abstraction of the spatial matching results hierarchical filtering techniques are used for refining the virtual properties. These approaches focus on two main application areas which are product model and Level of Detail (LoD). For the eMM suggested in this thesis a rule based interoperability method between arbitrary data models of spatial domain has been developed. The implementation of this method enables transaction of data in spatial domains run loss less. The system architecture and the implementation which has been applied on the case study of this thesis namely infrastructure and geospatial data models are described in chapter 5. Achieving afore mentioned aims results in reducing the whole project lifecycle costs, increasing reliability of the comprehensive fundamental information, and consequently in independent, cost-effective, aesthetically pleasing, and environmentally sensitive infrastructure design.:ABSTRACT 4 KEYWORDS 7 TABLE OF CONTENT 8 LIST OF FIGURES 9 LIST OF TABLES 11 LIST OF ABBREVIATION 12 INTRODUCTION 13 1.1. A GENERAL VIEW 14 1.2. PROBLEM STATEMENT 15 1.3. OBJECTIVES 17 1.4. APPROACH 18 1.5. STRUCTURE OF THESIS 18 INTEROPERABILITY IN INFRASTRUCTURE ENGINEERING 20 2.1. STATE OF INTEROPERABILITY 21 2.1.1. Interoperability of GIS and BIM 23 2.1.2. Interoperability of GIS and Infrastructure 25 2.2. MAIN CHALLENGES AND RELATED WORK 27 2.3. INFRASTRUCTURE MODELING IN GEOSPATIAL CONTEXT 29 2.3.1. LamdXML: Infrastructure Data Standards 32 2.3.2. CityGML: Geospatial Data Standards 33 2.3.3. LandXML and CityGML 36 2.4. INTEROPERABILITY AND MULTIMODEL TECHNOLOGY 39 2.5. LIMITATIONS OF EXISTING APPROACHES 41 INFRASTRUCTURE INFORMATION MODELLING 44 3.1. MULTI MODEL FOR GEOSPATIAL AND INFRASTRUCTURE DATA MODELS 45 3.2. LINKING APPROACH, QUERYING AND FILTERING 48 3.2.1. Virtual Properties via Link Model 49 3.3. MULTI MODEL AS AN INTERDISCIPLINARY METHOD 52 3.4. USING LEVEL OF DETAIL (LOD) FOR FILTERING 53 SPATIAL MODELLING AND PROCESSING 58 4.1. SPATIAL IDENTIFIERS 59 4.1.1. Spatial Indexes 60 4.1.2. Tree-Based Spatial Indexes 61 4.2. NEAREST NEIGHBORHOOD AS A BASIC LINK METHOD 63 4.3. HIERARCHICAL FILTERING 70 4.4. OTHER FUNCTIONAL LINK METHODS 75 4.5. ADVANCES AND LIMITATIONS OF FUNCTIONAL LINK METHODS 76 IMPLEMENTATION OF THE PROPOSED IIM METHOD 77 5.1. IMPLEMENTATION 78 5.2. CASE STUDY 83 CONCLUSION 89 6.1. SUMMERY 90 6.2. DISCUSSION OF RESULTS 92 6.3. FUTURE WORK 93 BIBLIOGRAPHY 94 7.1. BOOKS AND PAPERS 95 7.2. WEBSITES 10

Application of CRISPR-Cas9 genome editing systems for improving oilseed rape (Brassica napus) disease resistance against Verticillium longisporum

Modern agriculture requires innovative techniques to advance established strategies in breeding. Traditional approaches have their limitations and are primarily based on the availability of a broad genetic spectrum and the selection of suitable genotypes to improve the desired characteristics. One of these characteristics is the improvement of resistance to biotic stresses or pathogens. In order to achieve this goal in crops with a narrow genetic base such as Brassica napus new strategies are required. An example for this is the disruption of plant factors that are required by the pathogen for a successful colonization of the host (susceptibility factors). Verticillium wilt is caused by the soil-borne and hemi-biotrophic fungus Verticillium longisporum, which is one of the most common fungal diseases in rapeseed cultivation. The disease leads to premature ripening and can cause considerable yield losses. The methods for disease management are very limited. Countermeasures are mainly based on soil hygiene or prevention strategies to reduce the number of spores in the soil. The genetic resources for resistance breeding are limited and no real resistance has been discovered so far. Susceptibility factors in combination with genome modification based on CRISPR/Cas9 can be used as a source of recessive resistance. CRISPR/Cas9 is the most promising system for targeted mutagenesis with the advantage of easy assembly and use as well as multiplexing. The knockout of target genes is possible by the induction of small InDels caused by non-homologous end joining (NHEJ) after a double-strand break in the target site. Another approach possible through this technology is the introduction of a repair template for homology directed repair (HDR), which allows the nucleotide sequence to be altered without disrupting the gene function. In this study we adapt several vector systems containing different nucleases and promoters for application in Brassica napus. After successful establishment of our expression cassettes, the focus relied on the knockout of the candidate genes BnCRT1a and BnHVA22c, which are involved in the V. longisporum -B. napus interaction. Loss-of-function genotypes for the genes BnCRT1a and BnHVA22c were generated and infected with V. longisporum. In addition to this NHEJ approach, miRNA binding sites of fungal miRNAs in the host genome are modified using the HDR approach without affecting the function for the genes BnAGO1 and BnTAO1. For this purpose, the viral genome of the Bean Yellow Dwarf Virus was adapted for use in B. napus hairy roots. In summary, all loss-of-function genotypes showed a greatly reduced expression of symptoms and growth inhibition. These results support our working hypothesis that CRT1a and HVA22c may induce resistance to V. longisporum in their mutated state. Following experiments focused on the function of these genes in plants. Unfortunately, no significant differences in the expression profile of marker genes for molecular and physiological processes between mutants and wild type were found. Only the ethylene marker gene ETR2 showed increased expression in knockout genotypes in the uninfected state, which is consistent with expression data from A. thaliana. The analysis of co-regulated genes, which play a possible role in protein folding / ER stress (for CRT1a) or vesicle transport / callose closure of plasmodesmata (for HVA22c), showed no difference between mutants and the wild type as well. The vector systems for the HDR-based approach were successfully implemented and viral replicons of the Bean Yellow Dwarf Virus could be detected within the cell. The miRNA binding sites in the genes BnAGO1 and BnTAO1, which are used by V. longisporum, were the target of our HDR approach. No positive HDR events could be identified that would be indicated by a sequence exchange. Overall, this work showed that the use of CRISPR/Cas in combination with susceptibility factors is a valuable strategy for generating recessive resistance to pathogens. In the future, this tool can be integrated into existing breeding methods, especially for crops with limited genetic resources

STATISTICS IN THE BILLERA-HOLMES-VOGTMANN TREESPACE

This dissertation is an effort to adapt two classical non-parametric statistical techniques, kernel density estimation (KDE) and principal components analysis (PCA), to the Billera-Holmes-Vogtmann (BHV) metric space for phylogenetic trees. This adaption gives a more general framework for developing and testing various hypotheses about apparent differences or similarities between sets of phylogenetic trees than currently exists. For example, while the majority of gene histories found in a clade of organisms are expected to be generated by a common evolutionary process, numerous other coexisting processes (e.g. horizontal gene transfers, gene duplication and subsequent neofunctionalization) will cause some genes to exhibit a history quite distinct from the histories of the majority of genes. Such “outlying” gene trees are considered to be biologically interesting and identifying these genes has become an important problem in phylogenetics. The R sofware package kdetrees, developed in Chapter 2, contains an implementation of the kernel density estimation method. The primary theoretical difficulty involved in this adaptation concerns the normalizion of the kernel functions in the BHV metric space. This problem is addressed in Chapter 3. In both chapters, the software package is applied to both simulated and empirical datasets to demonstrate the properties of the method. A few first theoretical steps in adaption of principal components analysis to the BHV space are presented in Chapter 4. It becomes necessary to generalize the notion of a set of perpendicular vectors in Euclidean space to the BHV metric space, but there some ambiguity about how to best proceed. We show that convex hulls are one reasonable approach to the problem. The Nye-PCA- algorithm provides a method of projecting onto arbitrary convex hulls in BHV space, providing the core of a modified PCA-type method