Proteins are the fundamental machinery that enables the functions of life. It is critical to understand them not just for basic biology, but also to enable medical advances. The field of protein structure prediction is concerned with developing computational techniques to predict protein structure and function from a protein’s amino acid sequence, encoded for directly in DNA, alone. Despite much progress since the first computational models in the late 1960’s, techniques for the prediction of protein structure still cannot reliably produce structures of high enough accuracy to enable desired applications such as rational drug design. Protein structure refinement is the process of modifying a predicted model of a protein to bring it closer to its native state. In this dissertation a protein structure refinement technique, that of potential energy minimization using hybrid molecular mechanics/knowledge based potential energy functions is examined in detail. The generation of the knowledge-based component is critically analyzed, and in the end, a potential that is a modest improvement over the original is presented. This dissertation also examines the task of protein structure comparison. In evaluating various protein structure prediction techniques, it is crucial to be able to compare produced models against known structures to understand how well the technique performs. A novel technique is proposed that allows an in-depth yet intuitive evaluation of the local similarities between protein structures. Based on a graph analysis of pairwise atomic distance similarities, multiple regions of structural similarity can be identified between structures independently of relative orientation. Multidomain structures can be evaluated and this technique can be combined with global measures of similarity such as the global distance test. This method of comparison is expected to have broad applications in rational drug design, the evolutionary study of protein structures, and in the analysis of the protein structure prediction effort.

In past decades, the expectation of synergy has fueled many thousands of mergers and acquisitions. Meanwhile, economists and analysts have reported a large proportion of merger failures. This apparent contradiction has provided researchers with a rich source of studies. One of the likely causes of a merger failure is the “people factor”. Revolving around the axis of mergers and acquisitions, the peoples affected are, on the one side, the stockholders, top management, and economists who “talk the project” and tend to have a positive attitude and on the other side, the people who “walk the project” – the employees - who have a more hesitant attitude. / This empirical study adopted the construct of Psychological Contracts to measure the expectations of employees who are influenced by mergers and acquisitions. Based on this construct, a model was developed to study employees’ behaviour after a merger, examining it from a multitude of dimensions. Using the PLS-Graph analysis tools, the model was tested with the aim of assessing the factors’ impact on employees’ behaviour. Apart from the direct causal relationship between two variables, the indirect effects caused by other variables are assessed as well. / The first contribution made by this research is the fact that it examines the relevance of a psychological contract in a non-Western geographical region. Next, the study clearly confirms some of the existing conceptualizations regarding psychological contracts and reveals some additional insights, particularly in relation to the consideration of psychological contracts in a non-Western socio-cultural context. / The research aspires to generalize the model for predicting the post-merger behaviour of employees anywhere, across any industry, business segment and profession.

Obesity is associated with structural and functional alterations in brain areas that are often functionally distinct and anatomically distant. This suggests that obesity is associated with differences in functional connectivity of regions distributed across the brain. However, studies addressing whole brain functional connectivity in obesity remain scarce. Here, we compared voxel-wise degree centrality and eigenvector centrality between participants with obesity (n=20) and normal-weight controls (n=21). We analyzed resting state and task-related fMRI data acquired from the same individuals. Relative to normal-weight controls, participants with obesity exhibited reduced degree centrality in the right middle frontal gyrus in the resting-state condition. During the task fMRI condition, obese participants exhibited less degree centrality in the left middle frontal gyrus and the lateral occipital cortex along with reduced eigenvector centrality in the lateral occipital cortex and occipital pole. Our results highlight the central role of the middle frontal gyrus in the pathophysiology of obesity, a structure involved in several brain circuits signaling attention, executive functions and motor functions. Additionally, our analysis suggests the existence of task-dependent reduced centrality in occipital areas; regions with a role in perceptual processes and that are profoundly modulated by attention.

Chemical reactions can have a staggering amount of molecular complexity. Reaction mechanisms have been proposed with over one hundred elementary reaction steps that occur in the same system simultaneously. While several methods exist to simplify and make sense of the pathways and kinetics via which these reactions proceed, e.g., reaction graphs, sensitivity or flux analysis, microkinetic analysis, and comparison of energy landscapes, etc., these methods all have limitations and are often not able to capture a comprehensive picture of the kinetics of system. It has been found useful to view these mechanisms as a network, i.e., a reaction graph. These graphs enable the visualization of the pathways of the reaction and can provide an analytical tool for pathway and kinetic analysis. However, many of the specific graph-theoretic approaches in the literature are not the most suitable for kinetic analysis of complex mechanisms; as they are simply not based on rules that are rigorous enough to fully enumerate all the pathways or provide quantitative analysis of the reaction rates. Our Reaction Route (RR) Graph approach is different in that it depicts the mechanism by a graph that is consistent with all physical and chemical laws associated with reaction networks, particularly being consistent with mass and energy conservation, i.e., Kirchoff’s Flux Law (KFL) and Kirchoff’s Potential Law (KPL). Because of their adherence to these laws, RR Graphs are able to provide an accurate graph-theoretical tool not only for depicting all reactions routes as walks (hence the name RR Graph) but also for pruning mechanisms and allowing a simplified but accurate quantitative description of reaction rates. This adherence to KFL and KPL does mean that the construction and implementation of these graphs can be prohibitively difficult for large mechanisms. For large reaction systems,especially nonlinear mechanisms, it is not realistic to generate these graphs by hand. And although there exists an analytical solution to find a determinant matrix for the RR Graph of a mechanism, the process involves an exhaustive search for a solution which experiences a combinatorial explosion as the number of steps gets very large. This leads to the idea of developing an algorithm for a computer program that can determine how to generate these graphs automatically. Unfortunately, the same combinatorial explosion is present such that for a moderately sized twenty step mechanism, it could take an average computational processor over a decade to find a solution. We have determined, however, that this brute force combinatorial approach can be avoided if heuristics could be developed to bridge gaps in our knowledge of how these graphs are constructed. Thus, developing a better analytical approach and/or a tighter set of heuristics for a computer algorithm are the overarching goals of this work. To make progress toward developing such heuristics, a set of microkinetic mechanisms were analyzed with the notion that the realization of the RR Graphs would highlight a better approach to their construction and usage. In particular, a very large linear reaction system, a smaller linear system and two non-linear reaction systems were analyzed to develop insights into how each graph is manually constructed and analyzed. Furthermore, kinetic analysis was done for these mechanisms and compared to experimental data and other analytical tools to prove not only the validity of the RR Graphs, but also how they are a significant improvement over more commonly used approaches for mechanistic and kinetic analysis. Based on the lessons learned through a consideration of these examples, a set of heuristics are established and enumerated with the ultimate goal of developing an intuitive algorithm that can help automate drawing and kinetic analysis via RR Graphs of complex mechanisms.

This diploma work presents design and implementation of web information system for historians (called Electronic Encyclopaedia of History) with data model based on semantic network and of several tools for data analysis in such IS, using graph algorithms and graph mining methods.

Higher demands on database systems have lead to an increased popularity of certain database system types in some niche areas. One such niche area is graph networks, such as social networks or logistics networks. An analysis made on such networks often focus on complex relational patterns that sometimes can not be solved efficiently by traditional relational databases, which has lead to the infusion of some specialized non-relational database systems. Some of the database systems that have seen a surge in popularity in this area are graph database systems. This thesis presents a prototype of a logistics network-related service using a graph database management system called Neo4j, which currently is the most popular graph database management system in use. The logistics network covered by the service is based on existing data from PostNord, Sweden’s biggest provider of logistics solutions, and primarily focuses on customer support and business to business. By creating a prototype of the service this thesis strives to indicate some of the positive and negative aspects of a graph database system, as well as give an indication of how a service using a graph database system could be created. The results indicate that Neo4j is very intuitive and easy to use, which would make it optimal for prototyping and smaller systems, but due to the used evaluation method more research in this area would need to be carried out in order to confirm these conclusions. / Högre krav på databassystem har lett till en ökad popularitet för vissa databassystemstyper i några nischområden. Ett sådant nischområde är grafnätverk, såsomsociala nätverk eller logistiknätverk. Analyser på grafnätverk fokuserar ofta påkomplexa relationsmönster som ibland inte kan lösas effektivt av traditionella relationsdatabassystem, vilket har lett till att vissa specialiserade icke-relationella databassystem har blivit populära alternativ. Många av de populära databassystemen inom detta område är grafdatabassystem. Detta arbete presenterar en prototyp av en logistiknätverksrelaterad tjänst som använder sig av ett grafdatabashanteringssystem som heter Neo4j, vilket är det mest använda grafdatabashanteringssystemet. Logistiknätverket som täcks av tjänsten är baserad på existerande data från PostNord, Sveriges ledande leverantör av logistiklösningar, och fokuserar primärt på kundsupport och företagsrelaterad analys. Genom att skapa en prototyp av tjänsten strävar detta arbete efter att uppvisa vissa av de positiva och negativa aspekterna av ett grafdatabashanteringssystem samt att visa hur en tjänst kan skapas genom att använda ett grafdatabashanteringssystem. Resultaten indikerar att Neo4j är väldigt intuitivt och lättanvänt, vilket skulle göra den optimal för prototyping och mindre system, men på grund av den använda evalueringsmetoden så behöver mer forskning inom detta område utföras innan dessa slutsatser kan bekräftas.

Developing nonparametric statistical methods and inference procedures for high-dimensional large data have been a challenging frontier problem of statistics. To attack this problem, in recent years, a clear rising trend has been observed with a radically different viewpoint--``Graph-based Nonparametrics," which is the main research focus of this dissertation. The basic idea consists of two steps: (i) representation step: code the given data using graphs, (ii) analysis step: apply statistical methods on the graph-transformed problem to systematically tackle various types of data structures. Under this general framework, this dissertation develops two major research directions. Chapter 2—based on Mukhopadhyay and Wang (2019a)—introduces a new nonparametric method for high-dimensional k-sample comparison problem that is distribution-free, robust, and continues to work even when the dimension of the data is larger than the sample size. The proposed theory is based on modern LP-nonparametrics tools and unexplored connections with spectral graph theory. The key is to construct a specially-designed weighted graph from the data and to reformulate the k-sample problem into a community detection problem. The procedure is shown to possess various desirable properties along with a characteristic exploratory flavor that has practical consequences. The numerical examples show surprisingly well performance of our method under a broad range of realistic situations. Chapter 3—based on Mukhopadhyay and Wang (2019b)—revisits some foundational questions about network modeling that are still unsolved. In particular, we present unified statistical theory of the fundamental spectral graph methods (e.g., Laplacian, Modularity, Diffusion map, regularized Laplacian, Google PageRank model), which are often viewed as spectral heuristic-based empirical mystery facts. Despite half a century of research, this question has been one of the most formidable open issues, if not the core problem in modern network science. Our approach integrates modern nonparametric statistics, mathematical approximation theory (of integral equations), and computational harmonic analysis in a novel way to develop a theory that unifies and generalizes the existing paradigm. From a practical standpoint, it is shown that this perspective can provide adequate guidance for designing next-generation computational tools for large-scale problems. As an example, we have described the high-dimensional change-point detection problem. Chapter 4 discusses some further extensions and application of our methodologies to regularized spectral clustering and spatial graph regression problems. The dissertation concludes with the a discussion of two important areas of future studies. / Statistics

Wikipedia is a multilingual encyclopedia written collaboratively by volunteers online, and it is now the largest, most visited encyclopedia in existence. Wikipedia has arisen through the self-organized collaboration of contributors, and since its launch in January 2001, its potential as a research resource has become apparent to scientists, its appeal lies in the fact that it strikes a middle ground between accurate, manually created, limited-coverage resources, and noisy knowledge mined from the web. For this reason, Wikipedia's content has been exploited for a variety of applications: to build knowledge bases, to study interactions between users on the Internet, and to investigate social and cultural issues such as gender bias in history, or the spreading of information. Similarly to what happened for the Web at large, a structure has emerged from the collaborative creation of Wikipedia: its articles contain hundreds of millions of links. In Wikipedia parlance, these internal links are called wikilinks. These connections explain the topics being covered in articles and provide a way to navigate between different subjects, contextualizing the information, and making additional information available. In this thesis, we argue that the information contained in the link structure of Wikipedia can be harnessed to gain useful insights by extracting it with dedicated algorithms. More prosaically, in this thesis, we explore the link structure of Wikipedia with new methods. In the first part, we discuss in depth the characteristics of Wikipedia, and we describe the process and challenges we have faced to extract the network of links. Since Wikipedia is available in several language editions and its entire edition history is publicly available, we have extracted the wikilink network at various points in time, and we have performed data integration to improve its quality. In the second part, we show that the wikilink network can be effectively used to find the most relevant pages related to an article provided by the user. We introduce a novel algorithm, called CycleRank, that takes advantage of the link structure of Wikipedia considering cycles of links, thus giving weight to both incoming and outgoing connections, to produce a ranking of articles with respect to an article chosen by the user. In the last part, we explore applications of CycleRank. First, we describe the Engineroom EU project, where we faced the challenge to find which were the most relevant Wikipedia pages connected to the Wikipedia article about the Internet. Finally, we present another contribution using Wikipedia article accesses to estimate how the information about diseases propagates. In conclusion, with this thesis, we wanted to show that browsing Wikipedia's wikilinks is not only fascinating and serendipitous, but it is an effective way to extract useful information that is latent in the user-generated encyclopedia.

RNA-Seq is an increasingly popular approach to transcriptome profiling that uses the capabilities of next generation sequencing technologies and provides better measurement of levels of transcripts and their isoforms. In this thesis, we apply RNA-Seq protocol and transcriptome quantification to estimate gene expression and pathway activity levels. We present a novel method, called IsoDE, for differential gene expression analysis based on bootstrapping. In the first version of IsoDE, we compared the tool against four existing methods: Fisher's exact test, GFOLD, edgeR and Cuffdiff on RNA-Seq datasets generated using three different sequencing technologies, both with and without replicates. We also introduce the second version of IsoDE which runs 10 times faster than the first implementation due to some in-memory processing applied to the underlying gene expression frequencies estimation tool and we also perform more optimization on the analysis. The second part of this thesis presents a set of tools to differentially analyze metabolic pathways from RNA-Seq data. Metabolic pathways are series of chemical reactions occurring within a cell. We focus on two main problems in metabolic pathways differential analysis, namely, differential analysis of their inferred activity level and of their estimated abundance. We validate our approaches through differential expression analysis at the transcripts and genes levels and also through real-time quantitative PCR experiments. In part Four, we present the different packages created or updated in the course of this study. We conclude with our future work plans for further improving IsoDE 2.0.

How do we find patterns and anomalies, on graphs with billions of nodes and edges, which do not fit in memory? How to use parallelism for such Tera- or Peta-scale graphs? In this thesis, we propose PEGASUS, a large scale graph mining system implemented on the top of the HADOOP platform, the open source version of MAPREDUCE. PEGASUS includes algorithms which help us spot patterns and anomalous behaviors in large graphs. PEGASUS enables the structure analysis on large graphs. We unify many different structure analysis algorithms, including the analysis on connected components, PageRank, and radius/diameter, into a general primitive called GIM-V. GIM-V is highly optimized, achieving good scale-up on the number of edges and available machines. We discover surprising patterns using GIM-V, including the 7-degrees of separation in one of the largest publicly available Web graphs, with 7 billion edges. PEGASUS also enables the inference and the spectral analysis on large graphs. We design an efficient distributed belief propagation algorithm which infer the states of unlabeled nodes given a set of labeled nodes. We also develop an eigensolver for computing top k eigenvalues and eigenvectors of the adjacency matrices of very large graphs. We use the eigensolver to discover anomalous adult advertisers in the who-follows-whom Twitter graph with 3 billion edges. In addition, we develop an efficient tensor decomposition algorithm and use it to analyze a large knowledge base tensor. Finally, PEGASUS allows the management of large graphs. We propose efficient graph storage and indexing methods to answer graph mining queries quickly. We also develop an edge layout algorithm for better compressing graphs.