La maladie de Huntington est une maladie neurodégénérative héréditaire qui est devenue un modèle d'étude pour comprendre la physiopathologie des maladies du cerveau associées à la production de protéines mal conformées et à la neurodégénérescence. Bien que plusieurs mécanismes aient été mis en avant pour cette maladie, dont plusieurs seraient aussi impliqués dans des pathologies plus fréquentes comme la maladie d’Alzheimer ou la maladie de Parkinson, nous ne savons toujours pas quels sont les mécanismes ou les profils moléculaires qui déterminent fondamentalement la dynamique des processus de dysfonction et de dégénérescence neuronale dans cette maladie. De même, nous ne savons toujours pas comment le cerveau peut résister aussi longtemps à la production de protéines mal conformées, ce qui suggère en fait que ces protéines ne présentent qu’une toxicité modérée ou que le cerveau dispose d'une capacité de compensation et de résilience considérable. L'hypothèse de mon travail de thèse est que l'intégration de données génomiques et transcriptomiques au travers des modèles qui récapitulent différentes phases biologiques de la maladie de Huntington peut permettre de répondre à ces questions. Dans cette optique, l'utilisation des réseaux de gènes et la mise en application de concepts issus de la théorie des graphes sont particulièrement bien adaptés à l'intégration de données hétérogènes, au travers des modèles et au travers des espèces. Les résultats de mon travail suggèrent que l'altération précoce (avant les symptômes, avant la mort cellulaire) et éventuellement dès le développement cérébral) des grandes voies de développement et de maintenance neuronale, puis la persistance voire l'aggravation de ces effets, sont à la base des processus physiopathologiques qui conduisent à la dysfonction puis à la mort neuronale. Ces résultats permettent aussi de prioriser des gènes et de générer des hypothèses fortes sur les cibles thérapeutiques les plus intéressantes à étudier d'un point de vue expérimental. En conclusion, mes recherches ont un impact à la fois fondamental et translationnel sur l'étude de la maladie de Huntington, permettant de dégager des méthodes d'analyse et des hypothèses qui pourraient avoir valeur thérapeutique pour les maladies neurodégénératives en général. / Huntington’s disease is a hereditary neurodegenerative disease that has become a model to understand physiopathological mechanisms associated to misfolded proteins that ocurs in brain diseases. Despite exciting findings that have uncover pathological mechanisms occurring in this disease and that might also be relevant to Alzheimer’s disease and Parkinson’s disease, we still do not know yet which are the mechanisms and molecular profiles that rule the dynamic of neurodegenerative processes in Huntington’s disease. Also, we do not understand clearly how the brain resist over such a long time to misfolded proteins, which suggest that the toxicity of these proteins is mild, and that the brain have exceptional compensation capacities. My work is based on the hypothesis that integration of ‘omics’ data from models that depicts various stages of the disease might be able to give us clues to answer these questions. Within this framework, the use of network biology and graph theory concepts seems particularly well suited to help us integrate heterogeneous data across models and species. So far, the outcome of my work suggest that early, pre-symptomatic alterations of signaling pathways and cellular maintenance processes, and persistency and worthening of these phenomenon are at the basis of physiopathological processes that lead to neuronal dysfunction and death. These results might allow to prioritize targets and formulate new hypotheses that are interesting to further study and test experimentally. To conclude, this work shall have a fundamental and translational impact to the field of Huntington’s disease, by pinpointing methods and hypotheses that could be valuable in a therapeutic perspective.

Dans cette thèse, nous étudions les graphes aléatoires en utilisant des outils de la théorie des matrices aléatoires et l’analyse probabilistique afin de résoudre des problèmes clefs dans le domaine des réseaux complexes et Big Data. Le premier problème qu’on considère est de détecter un sous graphe Erdős–Rényi G(m,p) plante dans un graphe Erdős–Rényi G(n,q). Nous dérivons les distributions d’une statistique basée sur les propriétés spectrales d’une matrice définie du graphe. Ensuite, nous considérons le problème de la récupération des sommets du sous graphe en présence de l’information supplémentaire. Pour cela nous utilisons l’algorithme «Belief Propagation». Le BP sans informations supplémentaires ne réussit à la récupération qu’avec un SNR effectif lambda au-delà d’un seuil. Nous prouvons qu’en présence des informations supplémentaires, ce seuil disparaît et le BP réussi pour n’importe quel lambda. Finalement, nous dérivons des expressions asymptotiques pour PageRank sur une classe de graphes aléatoires non dirigés appelés « fast expanders », en utilisant des techniques théoriques à la matrice aléatoire. Nous montrons que PageRank peut être approché pour les grandes tailles du graphe comme une combinaison convexe du vecteur de dégré normalisé et le vecteur de personnalisation du PageRank, lorsque le vecteur de personnalisation est suffisamment délocalisé. Par la suite, nous caractérisons les formes asymptotiques de PageRank sur le Stochastic Block Model (SBM) et montrons qu’il contient un terme de correction qui est fonction de la structure de la communauté. / In this thesis, we study random graphs using tools from Random Matrix Theory and probability to tackle key problems in complex networks and Big Data. First we study graph anomaly detection. Consider an Erdős-Rényi (ER) graph with edge probability q and size n containing a planted subgraph of size m and probability p. We derive a statistical test based on the eigenvalue and eigenvector properties of a suitably defined matrix to detect the planted subgraph. We analyze the distribution of the derived test statistic using Random Matrix Theoretic techniques. Next, we consider subgraph recovery in this model in the presence of side-information. We analyse the effect of side-information on the detectability threshold of Belief Propagation (BP) applied to the above problem. We show that BP correctly recovers the subgraph even with noisy side-information for any positive value of an effective SNR parameter. This is in contrast to BP without side-information which requires the SNR to be above a certain threshold. Finally, we study the asymptotic behaviour of PageRank on a class of undirected random graphs called fast expanders, using Random Matrix Theoretic techniques. We show that PageRank can be approximated for large graph sizes as a convex combination of the normalized degree vector and the personalization vector of the PageRank, when the personalization vector is sufficiently delocalized. Subsequently, we characterize asymptotic PageRank on Stochastic Block Model (SBM) graphs, and show that it contains a correction term that is a function of the community structure.

To view the electricity supply in our society as just sockets mountedin our walls with a constant voltage output is far from the truth. Inreality, the power system supplying the electricity or the grid, is themost complex man-made dynamical system there is. It demands severecontrol and safety measures to ensure a reliable supply of electric power.Throughout the world, incidents of widespread power grid failures havebeen continuously reported. The state where electricity delivery to customersis terminated by a disturbance is called a blackout. From a stateof seemingly stable operating conditions, the grid can fast derail intoan uncontrollable state due to cascading failures. Transmission linesbecome automatically disconnected due to power flow redirections andparts of the grid become isolated and islands are formed. An islandedsub-grid incapable of maintaining safe operation conditions experiencesa blackout. A widespread blackout is a rare, but an extremely costlyand hazardous event for society.During recent years, many methods to prevent these kinds of eventshave been suggested. Controlled islanding has been a commonly suggestedstrategy to save the entire grid or parts of the grid from a blackout.Controlled islanding is a strategy of emergency control of a powergrid, in which the grid is intentionally split into a set of islanded subgridsfor avoiding an entire collapse. The key point in the strategy is todetermine appropriate separation boundaries, i.e. the set of transmissionlines separating the grid into two or more isolated parts.The power grid exhibits highly nonlinear response in the case oflarge failures. Therefore, this thesis proposes a new controlled islandingmethod for power grids based on the nonlinear Koopman Mode Analysis(KMA). The KMA is a new analyzing technique of nonlinear dynamicsbased on the so-called Koopman operator. Based on sampled data followinga disturbance, KMA is used to identify suitable partitions of thegrid.The KMA-based islanding method is numerically investigated withtwo well-known test systems proposed by the Institute of Electrical andElectronics Engineers (IEEE). By simulations of controlled islanding inthe test system, it is demonstrated that the grid’s response following afault can be improved with the proposed method.The proposed method is compared to a method of partitioning powergrids based on spectral graph theory which captures the structural propertiesof a network. It is shown that the intrinsic structural propertiesof a grid characterized by spectral graph theory are also captured by theKMA. This is shown both by numerical simulations and a theoreticalanalysis.

Spectral graph theory widely increases the interests in not only discovering new properties of well known graphs but also proving the well known properties for the new type of graphs. In fact all spectral properties of proverbial graphs are not acknowledged to us and in other hand due to the structure of nature, new classes of graphs are required to explain the phenomena around us and the spectral properties of these graphs can tell us more about the structure of them. These both themes are the body of our work here. We introduce here three models of random graphs and show that the eigenvalue counting function of Laplacians on these graphs has exponential decay bound. Since our methods heavily depend on the first nonzero eigenvalue of Laplacian, we study also this eigenvalue for the graph in both random and nonrandom cases.

This paper was written as a bachelor thesis in mathematics. We study adjacency matrices and their eigenvalues to investigate what properties of the corresponding graphs can be determined by those eigenvalues, the spectrum of the graph. The question of which graphs are uniquely determined by their spectra is also covered. Later on we study some methods of finding examples of graphs with shared spectra, also referred to as cospectral graphs.

[pt] O estudo de desvios, e em particular grandes desvios, tem uma história longa na teoria de probabilidade. Nas últimas décadas muitos artigos consideraram essas questões no contexto de subgrafos de grafos aleatórios G(n, p) e G(n, m). Esta dissertação considera a cauda inferior para o número de triângulos no grafo aleatório G(n, m). Duas abordagens estão consideradas: Martingales, a partir artigo de Christina Goldschmidt, Simon Griffiths e Alex Scott; e Teoria Espectral de Grafos, a partir do artigo de Joe Neeman, Charles Radin e Lorenzo Sadun. Essas duas abordagens conseguem encontrar o comportamento da cauda em dois regimes diferentes. Na dissertação discutiremos a visão geral do artigo de Goldschmidt, Griffiths e Scott, e discutiremos em detalhes o artigo de Neeman, Radin e Sadun. Em particular, exploraremos a conexão entre a cauda inferior do número de triângulos e o comportamento dos autovalores mais negativos da matriz de adjacência. Veremos que a contagem tende a depender, essencialmente, do autovalor mais negativo. / [en] The study of deviations, and in particular large deviations, has a long history in Probability Theory. In recent decades many articles have considered these questions in the context of subgraphs of the random graphs G(n, p) and G(n, m). This dissertation considers the lower tail for the number of triangles in the random graph G(n, m). Two approaches are considered: Martingales, based on the article of Christina Goldschmidt, Simon Griffiths and Alex Scott; and Spectral Graph Theory, based on the article of Joe Neeman, Charles Radin and Lorenzo Sadun. These two approaches manage to find the behavior of the tail in two different regimes. In this dissertation we give an overview of the article of Goldschmidt, Griffiths and Scott, discuss in detail the article of artigo Neeman, Radin and Sadun. In particular, we shall explore the connection between the lower tail of the number of triangles and the behavior of the most negative eigenvalues of the adjacency matrix. We shall see that the triangle count tends to especially depend on the most negative eigenvalue.

This thesis deals with optimizing extremal eigenvalues of weighted graph Laplacian matrices. In general, the Laplacian matrix of a (weighted) graph is of particular importance in spectral graph theory and combinatorial optimization (e.g., graph partition like max-cut and graph bipartition). Especially the pioneering work of M. Fiedler investigates extremal eigenvalues of weighted graph Laplacians and provides close connections to the node- and edge-connectivity of a graph. Motivated by Fiedler, Göring et al. were interested in further connections between structural properties of the graph and the eigenspace of the second smallest eigenvalue of weighted graph Laplacians using a semidefinite optimization approach. By redistributing the edge weights of a graph, the following three optimization problems are studied in this thesis: maximizing the second smallest eigenvalue (based on the mentioned work of Göring et al.), minimizing the maximum eigenvalue and minimizing the difference of maximum and second smallest eigenvalue of the weighted Laplacian. In all three problems a semidefinite optimization formulation allows to interpret the corresponding semidefinite dual as a graph realization problem. That is, to each node of the graph a vector in the Euclidean space is assigned, fulfilling some constraints depending on the considered problem. Optimal realizations are investigated and connections to the eigenspaces of corresponding optimized eigenvalues are established. Furthermore, optimal realizations are closely linked to the separator structure of the graph. Depending on this structure, on the one hand folding properties of optimal realizations are characterized and on the other hand the existence of optimal realizations of bounded dimension is proven. The general bounds depend on the tree-width of the graph. In the case of minimizing the maximum eigenvalue, an important family of graphs are bipartite graphs, as an optimal one-dimensional realization may be constructed. Taking the symmetry of the graph into account, a particular optimal edge weighting exists. Considering the coupled problem, i.e., minimizing the difference of maximum and second smallest eigenvalue and the single problems, i.e., minimizing the maximum and maximizing the second smallest eigenvalue, connections between the feasible (optimal) sets are established.

Cette thèse s'inscrit dans la théorie des matrices aléatoires, à l'intersection avec la théorie des probabilités libres et des algèbres d'opérateurs. Elle s'insère dans une démarche générale qui a fait ses preuves ces dernières décennies : importer les techniques et les concepts de la théorie des probabilités non commutatives pour l'étude du spectre de grandes matrices aléatoires. On s'intéresse ici à des généralisations du théorème de liberté asymptotique de Voiculescu. Dans les Chapitres 1 et 2, nous montrons des résultats de liberté asymptotique forte pour des matrices gaussiennes, unitaires aléatoires et déterministes. Dans les Chapitres 3 et 4, nous introduisons la notion de fausse liberté asymptotique pour des matrices déterministes et certaines matrices hermitiennes à entrées sous diagonales indépendantes, interpolant les modèles de matrices de Wigner et de Lévy. / The thesis fits into the random matrix theory, in intersection with free probability and operator algebra. It is part of a general approach which is common since the last decades: using tools and concepts of non commutative probability in order to get general results about the spectrum of large random matrices. Where are interested here in generalization of Voiculescu's asymptotic freeness theorem. In Chapter 1 and 2, we show some results of strong asymptotic freeness for gaussian, random unitary and deterministic matrices. In Chapter 3 and 4, we introduce the notion of asymptotic false freeness for deterministic matrices and certain random matrices, Hermitian with independent sub-diagonal entries, interpolating Wigner and Lévy models.

This thesis deals with optimizing extremal eigenvalues of weighted graph Laplacian matrices. In general, the Laplacian matrix of a (weighted) graph is of particular importance in spectral graph theory and combinatorial optimization (e.g., graph partition like max-cut and graph bipartition). Especially the pioneering work of M. Fiedler investigates extremal eigenvalues of weighted graph Laplacians and provides close connections to the node- and edge-connectivity of a graph. Motivated by Fiedler, Göring et al. were interested in further connections between structural properties of the graph and the eigenspace of the second smallest eigenvalue of weighted graph Laplacians using a semidefinite optimization approach. By redistributing the edge weights of a graph, the following three optimization problems are studied in this thesis: maximizing the second smallest eigenvalue (based on the mentioned work of Göring et al.), minimizing the maximum eigenvalue and minimizing the difference of maximum and second smallest eigenvalue of the weighted Laplacian. In all three problems a semidefinite optimization formulation allows to interpret the corresponding semidefinite dual as a graph realization problem. That is, to each node of the graph a vector in the Euclidean space is assigned, fulfilling some constraints depending on the considered problem. Optimal realizations are investigated and connections to the eigenspaces of corresponding optimized eigenvalues are established. Furthermore, optimal realizations are closely linked to the separator structure of the graph. Depending on this structure, on the one hand folding properties of optimal realizations are characterized and on the other hand the existence of optimal realizations of bounded dimension is proven. The general bounds depend on the tree-width of the graph. In the case of minimizing the maximum eigenvalue, an important family of graphs are bipartite graphs, as an optimal one-dimensional realization may be constructed. Taking the symmetry of the graph into account, a particular optimal edge weighting exists. Considering the coupled problem, i.e., minimizing the difference of maximum and second smallest eigenvalue and the single problems, i.e., minimizing the maximum and maximizing the second smallest eigenvalue, connections between the feasible (optimal) sets are established.

We consider the problem of maximizing the second smallest eigenvalue of the weighted Laplacian of a (simple) graph over all nonnegative edge weightings with bounded total weight. We generalize this problem by introducing node significances and edge lengths. We give a formulation of this generalized problem as a semidefinite program. The dual program can be equivalently written as embedding problem. This is fifinding an embedding of the n nodes of the graph in n-space so that their barycenter is at the origin, the distance between adjacent nodes is bounded by the respective edge length, and the embedded nodes are spread as much as possible. (The sum of the squared norms is maximized.) We proof the following necessary condition for optimal embeddings. For any separator of the graph at least one of the components fulfills the following property: Each straight-line segment between the origin and an embedded node of the component intersects the convex hull of the embedded nodes of the separator. There exists always an optimal embedding of the graph whose dimension is bounded by the tree-width of the graph plus one. We defifine the rotational dimension of a graph. This is the minimal dimension k such that for all choices of the node significances and edge lengths an optimal embedding of the graph can be found in k-space. The rotational dimension of a graph is a minor monotone graph parameter. We characterize the graphs with rotational dimension up to two.:1 Introduction 1.1 Notations and Preliminaries 1.2 The Algebraic Connectivity 1.3 Two applications 1.4 Outline 2 The Embedding Problem 2.1 Semidefinite formulation 2.2 The dual as geometric embedding problem 2.3 Physical interpretation and examples 2.4 Formulation without fifixed barycenter 3 Geometrical Operations 3.1 Congruent transformations 3.2 Folding a flat halfspace 3.3 Folding and Collapsing 4 Structural properties of optimal embeddings 4.1 Separator-Shadow 4.2 Separators containing the origin 4.3 The tree-width bound 4.4 Application to trees 5 The Rotational Dimension of a graph 5.1 Defifinition and basic properties 5.2 Characterization of graphs with small rotational dimension 5.3 The Colin de Verdi ere graph parameter List of Figures Bibliography Theses