In this work we study several important properties of the 2-microlocal Besov and Triebel-Lizorkin spaces with variable integrability. Due to the richness of the weight sequence used to measure smoothness, this scale of function spaces incorporates a wide range of function spaces, of which we mention the spaces with variable smoothness. Within the existing characterizations of these spaces, the characterization via smooth atoms is undoubtedly one of the most used when it comes to obtain new results in varied directions. In this work we make use of such characterization to prove several embedding results, such as Sobolev, Franke and Jawerth embeddings, and also to study traces on hyperplanes. Despite the considerable benefits of resorting on the smooth atomic decomposition, there are still some limitations when one tries to use it in order to prove some specific results, such as pointwise multipliers and diffeomorphisms assertions. The non-smooth atomic characterization proved in this work overcome these problems, due to the weaker conditions of the (non-smooth) atoms. Moreover, it also allows us to give an intrinsic characterization of the 2-microlocal Besov and Triebel-Lizorkin spaces with variable integrability on the class of regular domains, in which connected bounded Lipschitz domains are included. / In dieser Arbeit untersuchen wir einige wichtige Eigenschaften der 2-microlokalen Besov und Triebel-Lizorkin Räume mit variabler Integrabilität. Weil die Glattheit hier mit einer reicher Gewichtsfolge gemessen wird, beinhaltet diese Skala von Funktionsräumen eine große Anzahl von Funktionsräumen, von denen wir die Räume mit variabler Glattheit erwähnen. Innerhalb der vorhandenen Charakterisierungen dieser Räume ist die Charakterisierung mit glatten Atomen zweifellos eine der am häufigsten verwendeten, um neue Ergebnisse in verschiedenen Richtungen zu erhalten. In dieser Arbeit verwenden wir eine solche Charakterisierung, um mehrere Einbettungsergebnisse zu bewiesen, wie Sobolev-Einbettungen und Einbettungen vom Franke-Jawerth Typ, und auch Spurresultate zu untersuchen. Trotz der beträchtlichen Vorteile des Rückgriffs auf die glatte Atomaren-Zerlegung gibt es immer noch einige Einschränkungen, wenn man versucht, sie zu verwenden, um einige spezifische Ergebnisse zu beweisen, wie beispielsweise punktweise Multiplikatoren und Diffeomorphismen-Assertionen. Die nichtglatte atomare Charakterisierung, die wir in dieser Arbeit beweisen, überwindet diese Probleme aufgrund der schwächeren Bedingungen von (nichtglatten) Atomen. Außerdem erlaubt es uns, eine Intrinsische Charakterisierung der 2-mikrolokalen Besov- und Triebel-Lizorkin-Räume mit variabler Integrabilität auf regulärer Gebieten zu geben.

<p>Research on graph representation learning (GRL) has made major strides over the past decade, with widespread applications in domains such as e-commerce, personalization, fraud & abuse, life sciences, and social network analysis. Despite its widespread success, fundamental questions on practices employed in modern day GRL have remained unanswered. Unraveling and advancing two such fundamental questions on the practices in modern day GRL forms the overarching theme of my thesis.</p> <p>The first part of my thesis deals with the mathematical foundations of GRL. GRL is used to solve tasks such as node classification, link prediction, clustering, graph classification, and so on, albeit with seemingly different frameworks (e.g. Graph neural networks for node/graph classification, (implicit) matrix factorization for link prediction/ clustering, etc.). The existence of very distinct frameworks for different graph tasks has puzzled researchers and practitioners alike. In my thesis, using group theory, I provide a theoretical blueprint that connects these seemingly different frameworks, bridging methods like matrix factorization and graph neural networks. With this renewed understanding, I then provide guidelines to better realize the full capabilities of these methods in a multitude of tasks.</p> <p>The second part of my thesis deals with cases where modeling real-world objects as a graph is an oversimplified description of the underlying data. Specifically, I look at two such objects (i) modeling hypergraphs (where edges encompass two or more vertices) and (ii) using GRL for predicting protein properties. Towards (i) hypergraphs, I develop a hypergraph neural network which takes advantage of the inherent sparsity of real world hypergraphs, without unduly sacrificing on its ability to distinguish non isomorphic hypergraphs. The designed hypergraph neural network is then leveraged to learn expressive representations of hyperedges for two tasks, namely hyperedge classification and hyperedge expansion. Experiments show that using our network results in improved performance over the current approach of converting the hypergraph into a dyadic graph and using (dyadic) GRL frameworks. Towards (ii) proteins, I introduce the concept of conditional invariances and leverage it to model the inherent flexibility present in proteins. Using conditional invariances, I provide a new framework for GRL which can capture protein-dependent conformations and ensures that all viable conformers of a protein obtain the same representation. Experiments show that endowing existing GRL models with my framework shows noticeable improvements on multiple different protein datasets and tasks.</p>

<p>The most important networks from different domains—such as Computing, Organization, Economic, Social, Academic, and Biology—are networks that change over time. For example, in an organization there are email and collaboration networks (e.g., different people or teams working on a document). Apart from the connectivity of the networks changing over time, they can contain attributes such as the topic of an email or message, contents of a document, or the interests of a person in an academic citation or a social network. Analyzing these dynamic networks can be critical in decision-making processes. For instance, in an organization, getting insight into how people from different teams collaborate, provides important information that can be used to optimize workflows.</p> <p><br></p> <p>Network generative models provide a way to study and analyze networks. For example, benchmarking model performance and generalization in tasks like node classification, can be done by evaluating models on synthetic networks generated with varying structure and attribute correlation. In this work, we begin by presenting our systemic study of the impact that graph structure and attribute auto-correlation on the task of node classification using collective inference. This is the first time such an extensive study has been done. We take advantage of a recently developed method that samples attributed networks—although static—with varying network structure jointly with correlated attributes. We find that the graph connectivity that contributes to the network auto-correlation (i.e., the local relationships of nodes) and density have the highest impact on the performance of collective inference methods.</p> <p><br></p> <p>Most of the literature to date has focused on static representations of networks, partially due to the difficulty of finding readily-available datasets of dynamic networks. Dynamic network generative models can bridge this gap by generating synthetic graphs similar to observed real-world networks. Given that motifs have been established as building blocks for the structure of real-world networks, modeling them can help to generate the graph structure seen and capture correlations in node connections and activity. Therefore, we continue with a study of motif evolution in <em>dynamic</em> temporal graphs. Our key insight is that motifs rarely change configurations in fast-changing dynamic networks (e.g. wedges intotriangles, and vice-versa), but rather keep reappearing at different times while keeping the same configuration. This finding motivates the generative process of our proposed models, using temporal motifs as building blocks, that generates dynamic graphs with links that appear and disappear over time.</p> <p><br></p> <p>Our first proposed model generates dynamic networks based on motif-activity and the roles that nodes play in a motif. For example, a wedge is sampled based on the likelihood of one node having the role of hub with the two other nodes being the spokes. Our model learns all parameters from observed data, with the goal of producing synthetic graphs with similar graph structure and node behavior. We find that using motifs and node roles helps our model generate the more complex structures and the temporal node behavior seen in real-world dynamic networks.</p> <p><br></p> <p>After observing that using motif node-roles helps to capture the changing local structure and behavior of nodes, we extend our work to also consider the attributes generated by nodes’ activities. We propose a second generative model for attributed dynamic networks that (i) captures network structure dynamics through temporal motifs, and (ii) extends the structural roles of nodes in motifs to roles that generate content embeddings. Our new proposed model is the first to generate synthetic dynamic networks and sample content embeddings based on motif node roles. To the best of our knowledge, it is the only attributed dynamic network model that can generate <em>new</em> content embeddings—not observed in the input graph, but still similar to that of the input graph. Our results show that modeling the network attributes with higher-order structures (e.g., motifs) improves the quality of the networks generated.</p> <p><br></p> <p>The generative models proposed address the difficulty of finding readily-available datasets of dynamic networks—attributed or not. This work will also allow others to: (i) generate networks that they can share without divulging individual’s private data, (ii) benchmark model performance, and (iii) explore model generalization on a broader range of conditions, among other uses. Finally, the evaluation measures proposed will elucidate models, allowing fellow researchers to push forward in these domains.</p>

Whole-exome and genome sequencing are widely used to diagnose individual patients. However, despite its success, this approach leaves many patients undiagnosed. This could be due to the need to discover more disease genes and variants or because disease phenotypes are novel and arise from a combination of variants of multiple known genes related to the disease. Recent rapid increases in available genomic, biomedical, and phenotypic data enable computational analyses, reducing the search space for disease-causing genes or variants and facilitating the prediction of causal variants. Therefore, artificial intelligence, data mining, machine learning, and deep learning are essential tools that have been used to identify biological interactions, including protein-protein interactions, gene-disease predictions, and variant--disease associations. Predicting these biological associations is a critical step in diagnosing patients with rare or complex diseases. In recent years, computational methods have emerged to improve gene-disease prioritization by incorporating phenotype information. These methods evaluate a patient's phenotype against a database of gene-phenotype associations to identify the closest match. However, inadequate knowledge of phenotypes linked with specific genes in humans and model organisms limits the effectiveness of the prediction. Information about gene product functions and anatomical locations of gene expression is accessible for many genes and can be associated with phenotypes through ontologies and machine-learning models. Incorporating this information can enhance gene-disease prioritization methods and more accurately identify potential disease-causing genes. This dissertation aims to address key limitations in gene-disease prediction and variant prioritization by developing computational methods that systematically relate human phenotypes that arise as a consequence of the loss or change of gene function to gene functions and anatomical and cellular locations of activity. To achieve this objective, this work focuses on crucial problems in the causative variant prioritization pipeline and presents novel computational methods that significantly improve prediction performance by leveraging large background knowledge data and integrating multiple techniques. Therefore, this dissertation presents novel approaches that utilize graph-based machine-learning techniques to leverage biomedical ontologies and linked biological data as background knowledge graphs. The methods employ representation learning with knowledge graphs and introduce generic models that address computational problems in gene-disease associations and variant prioritization. I demonstrate that my approach is capable of compensating for incomplete information in public databases and efficiently integrating with other biomedical data for similar prediction tasks. Moreover, my methods outperform other relevant approaches that rely on manually crafted features and laborious pre-processing. I systematically evaluate our methods and illustrate their potential applications for data analytics in biomedicine. Finally, I demonstrate how our prediction tools can be used in the clinic to assist geneticists in decision-making. In summary, this dissertation contributes to the development of more effective methods for predicting disease-causing variants and advancing precision medicine.