A machine learning approach to the unsupervised segmentation of mitochondria in subcellular electron microscopy data

Recent advances in cellular and subcellular microscopy demonstrated its potential towards unravelling the mechanisms of various diseases at the molecular level. The biggest challenge in both human- and computer-based visual analysis of micrographs is the variety of nanostructures and mitochondrial morphologies. The state-of-the-art is, however, dominated by supervised manual data annotation and early attempts to automate the segmentation process were based on supervised machine learning techniques which require large datasets for training. Given a minimal number of training sequences or none at all, unsupervised machine learning formulations, such as spectral dimensionality reduction, are known to be superior in detecting salient image structures. This thesis presents three major contributions developed around the spectral clustering framework which is proven to capture perceptual organization features. Firstly, we approach the problem of mitochondria localization. We propose a novel grouping method for the extracted line segments which describes the normal mitochondrial morphology. Experimental findings show that the clusters obtained successfully model the inner mitochondrial membrane folding and therefore can be used as markers for the subsequent segmentation approaches. Secondly, we developed an unsupervised mitochondria segmentation framework. This method follows the evolutional ability of human vision to extrapolate salient membrane structures in a micrograph. Furthermore, we designed robust non-parametric similarity models according to Gestaltic laws of visual segregation. Experiments demonstrate that such models automatically adapt to the statistical structure of the biological domain and return optimal performance in pixel classification tasks under the wide variety of distributional assumptions. The last major contribution addresses the computational complexity of spectral clustering. Here, we introduced a new anticorrelation-based spectral clustering formulation with the objective to improve both: speed and quality of segmentation. The experimental findings showed the applicability of our dimensionality reduction algorithm to very large scale problems as well as asymmetric, dense and non-Euclidean datasets

Hierarchical spectral clustering reveals brain size and shape changes in asymptomatic carriers of C9orf72

Traditional methods for detecting asymptomatic brain changes in neurodegenerative diseases such as Alzheimer\u27s disease or frontotemporal degeneration typically evaluate changes in volume at a predefined level of granularity, e.g. voxel-wise or in a priori defined cortical volumes of interest. Here, we apply a method based on hierarchical spectral clustering, a graph-based partitioning technique. Our method uses multiple levels of segmentation for detecting changes in a data-driven, unbiased, comprehensive manner within a standard statistical framework. Furthermore, spectral clustering allows for detection of changes in shape along with changes in size. We performed tensor-based morphometry to detect changes in the Genetic Frontotemporal dementia Initiative asymptomatic and symptomatic frontotemporal degeneration mutation carriers using hierarchical spectral clustering and compared the outcome to that obtained with a more conventional voxel-wise tensor- and voxel-based morphometric analysis. In the symptomatic groups, the hierarchical spectral clustering-based method yielded results that were largely in line with those obtained with the voxel-wise approach. In asymptomatic C9orf72 expansion carriers, spectral clustering detected changes in size in medial temporal cortex that voxel-wise methods could only detect in the symptomatic phase. Furthermore, in the asymptomatic and the symptomatic phases, the spectral clustering approach detected changes in shape in the premotor cortex in C9orf72. In summary, the present study shows the merit of hierarchical spectral clustering for data-driven segmentation and detection of structural changes in the symptomatic and asymptomatic stages of monogenic frontotemporal degeneration

Hierarchical spectral clustering reveals brain size and shape changes in asymptomatic carriers of <i>C9orf72</i>

Traditional methods for detecting asymptomatic brain changes in neurodegenerative diseases such as Alzheimer's disease or frontotemporal degeneration typically evaluate changes in volume at a predefined level of granularity, e.g. voxel-wise or in a priori defined cortical volumes of interest. Here, we apply a method based on hierarchical spectral clustering, a graph-based partitioning technique. Our method uses multiple levels of segmentation for detecting changes in a data-driven, unbiased, comprehensive manner within a standard statistical framework. Furthermore, spectral clustering allows for detection of changes in shape along with changes in size. We performed tensor-based morphometry to detect changes in the Genetic Frontotemporal dementia Initiative asymptomatic and symptomatic frontotemporal degeneration mutation carriers using hierarchical spectral clustering and compared the outcome to that obtained with a more conventional voxel-wise tensor- and voxel-based morphometric analysis. In the symptomatic groups, the hierarchical spectral clustering-based method yielded results that were largely in line with those obtained with the voxel-wise approach. In asymptomatic C9orf72 expansion carriers, spectral clustering detected changes in size in medial temporal cortex that voxel-wise methods could only detect in the symptomatic phase. Furthermore, in the asymptomatic and the symptomatic phases, the spectral clustering approach detected changes in shape in the premotor cortex in C9orf72. In summary, the present study shows the merit of hierarchical spectral clustering for data-driven segmentation and detection of structural changes in the symptomatic and asymptomatic stages of monogenic frontotemporal degeneration.© The Author(s) 2022. Published by Oxford University Press on behalf of the Guarantors of Brain

Diffusion, methods and applications

Tesis doctoral inédita leída en la Universidad Autónoma de Madrid, Escuela Politécnica Superior, Departamento de Ingeniería Informática. Fecha de lectura: junio de 2014Big Data, an important problem nowadays, can be understood in terms of a very large number of patterns, a very large pattern dimension or, often, both. In this thesis, we will concentrate on the high dimensionality issue, applying manifold learning techniques for visualizing and analyzing such patterns. The core technique will be Di usion Maps (DM) and its Anisotropic Di usion (AD) version, introduced by Ronald R. Coifman and his school at Yale University, and of which we will give a complete, systematic, compact and self-contained treatment. This will be done after a brief survey of previous manifold learning methods. The algorithmic contributions of the thesis will be centered in two computational challenges of di usion methods: the potential high cost of the similarity matrix eigenanalysis that is needed to define the di usion embedding coordinates, and the di culty of computing this embedding over new patterns not available for the initial eigenanalysis. With respect to the first issue, we will show how the AD set up can be used to skip it when looking for local models. In this case, local patterns will be selected through a k-Nearest Neighbors search using a properly defined local Mahalanobis distance, that enables neighbors to be found over the latent variable space underlying the AD model while we can work directly with the observable patterns and, thus, avoiding the potentially costly similarity matrix eigenanalysis. The second proposed algorithm, that we will call Auto-adaptative Laplacian Pyramids (ALP), focuses in the out-of-sample embedding extension and consists in a modification of the classical Laplacian Pyramids (LP) method. In this new algorithm the LP iterations will be combined with an estimate of the Leave One Out CV error, something that makes possible to directly define during training a criterion to estimate the optimal stopping point of this iterative algorithm. This thesis will also present several application contributions to important problems in renewable energy and medical imaging. More precisely, we will show how DM is a good method for dimensionality reduction of meteorological weather predictions, providing tools to visualize and describe these data, as well as to cluster them in order to define local models. In turn, we will apply our AD-based localized search method first to find the location in the human body of CT scan images and then to predict wind energy ramps on both individual farms and over the whole of Spain. We will see that, in both cases, our results improve on the current state of the art methods. Finally, we will compare our ALP proposal with the well-known Nyström method as well as with LP on two large dimensional problems, the time compression of meteorological data and the analysis of meteorological variables relevant in daily radiation forecasts. In both cases we will show that ALP compares favorably with the other approaches for out-of-sample extension problemsBig Data es un problema importante hoy en día, que puede ser entendido en términos de un amplio número de patrones, una alta dimensión o, como sucede normalmente, de ambos. Esta tesis se va a centrar en problemas de alta dimensión, aplicando técnicas de aprendizaje de subvariedades para visualizar y analizar dichos patrones. La técnica central será Di usion Maps (DM) y su versión anisotrópica, Anisotropic Di usion (AD), introducida por Ronald R. Coifman y su escuela en la Universidad de Yale, la cual va a ser tratada de manera completa, sistemática, compacta y auto-contenida. Esto se llevará a cabo tras un breve repaso de métodos previos de aprendizaje de subvariedades. Las contribuciones algorítmicas de esta tesis estarán centradas en dos de los grandes retos en métodos de difusión: el potencial alto coste que tiene el análisis de autovalores de la matriz de similitud, necesaria para definir las coordenadas embebidas; y la dificultad para calcular este mismo embedding sobre nuevos datos que no eran accesibles cuando se realizó el análisis de autovalores inicial. Respecto al primer tema, se mostrará cómo la aproximación AD se puede utilizar para evitar el cálculo del embedding cuando estamos interesados en definir modelos locales. En este caso, se seleccionarán patrones cercanos por medio de una búsqueda de vecinos próximos (k-NN), usando como distancia una medida de Mahalanobis local que permita encontrar vecinos sobre las variables latentes existentes bajo el modelo de AD. Todo esto se llevará a cabo trabajando directamente sobre los patrones observables y, por tanto, evitando el costoso cálculo que supone el cálculo de autovalores de la matriz de similitud. El segundo algoritmo propuesto, que llamaremos Auto-adaptative Laplacian Pyramids (ALP), se centra en la extensión del embedding para datos fuera de la muestra, y se trata de una modificación del método denominado Laplacian Pyramids (LP). En este nuevo algoritmo, las iteraciones de LP se combinarán con una estimación del error de Leave One Out CV, permitiendo definir directamente durante el periodo de entrenamiento, un criterio para estimar el criterio de parada óptimo para este método iterativo. En esta tesis se presentarán también una serie de contribuciones de aplicación de estas técnicas a importantes problemas en energías renovables e imágenes médicas. Más concretamente, se muestra como DM es un buen método para reducir la dimensión de predicciones del tiempo meteorológico, sirviendo por tanto de herramienta de visualización y descripción, así como de clasificación de los datos con vistas a definir modelos locales sobre cada grupo descrito. Posteriormente, se aplicará nuestro método de búsqueda localizada basado en AD tanto a la búsqueda de la correspondiente posición de tomografías en el cuerpo humano, como para la detección de rampas de energía eólica en parques individuales o de manera global en España. En ambos casos se verá como los resultados obtenidos mejoran los métodos del estado del arte actual. Finalmente se comparará el algoritmo de ALP propuesto frente al conocido método de Nyström y al método de LP, en dos problemas de alta dimensión: el problema de compresión temporal de datos meteorológicos y el análisis de variables meteorológicas relevantes para la predicción de la radiación diaria. En ambos casos se mostrará cómo ALP es comparativamente mejor que otras aproximaciones existentes para resolver el problema de extensión del embedding a puntos fuera de la muestr

Learning from complex networks

Graph Theory has proven to be a universal language for describing modern complex systems. The elegant theoretical framework of graphs drew the researchers' attention over decades. Therefore, graphs have emerged as a ubiquitous data structure in various applications where a relational characteristic is evident. Graph-driven applications are found, e.g., in social network analysis, telecommunication networks, logistic processes, recommendation systems, modeling kinetic interactions in protein networks, or the 'Internet of Things' (IoT) where modeling billions of interconnected web-enabled devices is of paramount importance. This thesis dives deep into the challenges of modern graph applications. It proposes a robustified and accelerated spectral clustering model in homogeneous graphs and novel transformer-driven graph shell models for attributed graphs. A new data structure is introduced for probabilistic graphs to compute the information flow efficiently. Moreover, a metaheuristic algorithm is designed to find a good solution to an optimization problem composed of an extended vehicle routing problem. The thesis closes with an analysis of trend flows in social media data. Detecting communities within a graph is a fundamental data mining task of interest in virtually all areas and also serves as an unsupervised preprocessing step for many downstream tasks. One most the most well-established clustering methods is Spectral Clustering. However, standard spectral clustering is highly sensitive to noisy input data, and the eigendecomposition has a high, cubic runtime complexity O(n^3). Tackling one of these problems often exacerbates the other. This thesis presents a new model which accelerates the eigendecomposition step by replacing it with a Nyström approximation. Robustness is achieved by iteratively separating the data into a cleansed and noisy part of the data. In this process, representing the input data as a graph is vital to identify parts of the data being well connected by analyzing the vertices' distances in the eigenspace. With the advances in deep learning architectures, we also observe a surge in research on graph representation learning. The message-passing paradigm in Graph Neural Networks (GNNs) formalizes a predominant heuristic for multi-relational and attributed graph data to learn node representations. In downstream applications, we can use the representations to tackle theoretical problems known as node classification, graph classification/regression, and relation prediction. However, a common issue in GNNs is known as over-smoothing. By increasing the number of iterations within the message-passing, the nodes' representations of the input graph align and become indiscernible. This thesis shows an efficient way of relaxing the GNN architecture by employing a routing heuristic in the general workflow. Specifically, an additional layer routes the nodes' representations to dedicated experts. Each expert calculates the representations according to their respective GNN workflow. The definitions of distinguishable GNNs result from k-localized views starting from a central node. This procedure is referred to as Graph Shell Attention (SEA), where experts process different subgraphs in a transformer-motivated fashion. Reliable propagation of information through large communication networks, social networks, or sensor networks is relevant to applications concerning marketing, social analysis, or monitoring physical or environmental conditions. However, social ties of friendship may be obsolete, and communication links may fail, inducing the notion of uncertainty in such networks. This thesis addresses the problem of optimizing information propagation in uncertain networks given a constrained budget of edges. A specialized data structure, called F-tree, addresses two NP-hard subproblems: the computation of the expected information flow and the optimal choice of edges. The F-tree identifies independent components of a probabilistic input graph for which the information flow can either be computed analytically and efficiently or for which traditional Monte-Carlo sampling can be applied independently of the remaining network. The next part of the thesis covers a graph problem from the Operations Research point of view. A new variant of the well-known vehicle routing problem (VRP) is introduced, where customers are served within a specific time window (TW), as well as flexible delivery locations (FL) including capacity constraints. The latter implies that each customer is scheduled in one out of a set of capacitated delivery service locations. Practically, the VRPTW-FL problem is relevant for applications in parcel delivery, routing with limited parking space, or, for example, in the scope of hospital-wide scheduling of physical therapists. This thesis presents a metaheuristic built upon a hybrid Adaptive Large Neighborhood Search (ALNS). Moreover, a backtracking mechanism in the construction phase is introduced to alter unsatisfactory decisions at early stages. In the computational study, hospital data is used to evaluate the utility of flexible delivery locations and various cost functions. In the last part of the thesis, social media trends are analyzed, which yields insights into user sentiment and newsworthy topics. Such trends consist of bursts of messages concerning a particular topic within a time frame, significantly deviating from the average appearance frequency of the same subject. This thesis presents a method to classify trend archetypes to predict future dissemination by investigating the dissemination of such trends in space and time. Generally, with the ever-increasing scale and complexity of graph-structured datasets and artificial intelligence advances, AI-backed models will inevitably play an important role in analyzing, modeling, and enhancing knowledge extraction from graph data.Die Graphentheorie hat sich zur einer universellen Sprache entwickelt, mit Hilfe derer sich moderne und komplexe Systeme und Zusammenhänge beschreiben lassen. Diese theoretisch elegante und gut fundierte Rahmenstruktur attrahierte über Dekaden hinweg die Aufmerksamkeit von Wissenschaftlern/-innen. In der heutigen Informationstechnologie-Landschaft haben sich Graphen längst zu einer allgegenwärtigen Datenstruktur in Anwendungen etabliert, innerhalb derer charakteristische Zusammenhangskomponenten eine zentrale Rolle spielen. Anwendungen, die über Graphen unterstützt werden, finden sich u.a. in der Analyse von sozialen Netzwerken, Telekommunikationsnetwerken, logistische Prozessverwaltung, Analyse von Empfehlungsdiensten, in der Modellierung kinetischer Interaktionen von Proteinstrukturen, oder auch im "Internet der Dinge" (engl.: 'Internet Of Things' (IoT)), welches das Zusammenspiel von abermillionen web-unterstützte Endgeräte abbildet und eine prädominierende Rolle für große IT-Unternehmen spielt. Diese Dissertation beleuchtet die Herausforderungen moderner Graphanwendungen. Im Bereich homogener Netzwerken wird ein beschleunigtes und robustes spektrales Clusteringverfahren, sowie ein Modell zur Untersuchung von Teilgraphen mittels Transformer-Architekturen für attribuierte Graphen vorgestellt. Auf wahrscheinlichkeitsbasierten homogenen Netzwerken wird eine neue Datenstruktur eingeführt, die es erlaubt einen effizienten Informationsfluss innerhalb eines Graphen zu berechnen. Darüber hinaus wird ein Optimierungsproblem in Transportnetzwerken beleuchtet, sowie eine Untersuchung von Trendflüssen in sozialen Medien diskutiert. Die Untersuchung von Verbünden (engl.: 'Clusters') von Graphdaten stellt einen Eckpfeiler im Bereich der Datengewinnung dar. Die Erkenntnisse sind nahezu in allen praktischen Bereichen von Relevanz und dient im Bereich des unüberwachten Lernens als Vorverarbeitungsschritt für viele nachgeschaltete Aufgaben. Einer der weit verbreitetsten Methodiken zur Verbundanalyse ist das spektrale Clustering. Die Qualität des spektralen Clusterings leidet, wenn die Eingabedaten sehr verrauscht sind und darüber hinaus ist die Eigenwertzerlegung mit O(n^3) eine teure Operation und damit wesentlich für die hohe, kubische Laufzeitkomplexität verantwortlich. Die Optimierung von einem dieser Kriterien exazerbiert oftmals das verbleibende Kriterium. In dieser Dissertation wird ein neues Modell vorgestellt, innerhalb dessen die Eigenwertzerlegung über eine Nyström Annäherung beschleunigt wird. Die Robustheit wird über ein iteratives Verfahren erreicht, das die gesäuberten und die verrauschten Daten voneinander trennt. Die Darstellung der Eingabedaten über einen Graphen spielt hierbei die zentrale Rolle, die es erlaubt die dicht verbundenen Teile des Graphen zu identifizieren. Dies wird über eine Analyse der Distanzen im Eigenraum erreicht. Parallel zu neueren Erkenntnissen im Bereich des Deep Learnings lässt sich auch ein Forschungsdrang im repräsentativen Lernen von Graphen erkennen. Graph Neural Networks (GNN) sind eine neue Unterform von künstlich neuronalen Netzen (engl.: 'Artificial Neural Networks') auf der Basis von Graphen. Das Paradigma des sogenannten 'message-passing' in neuronalen Netzen, die auf Graphdaten appliziert werden, hat sich hierbei zur prädominierenden Heuristik entwickelt, um Vektordarstellungen von Knoten aus (multi-)relationalen, attribuierten Graphdaten zu lernen. Am Ende der Prozesskette können wir somit theoretische Probleme angehen und lösen, die sich mit Fragestellungen über die Klassifikation von Knoten oder Graphen, über regressive Ausdrucksmöglichkeiten bis hin zur Vorhersage von relationaler Verbindungen beschäftigen. Ein klassisches Problem innerhalb graphischer neuronaler Netze ist bekannt unter der Terminologie des 'over-smoothing' (dt.: 'Überglättens'). Es beschreibt, dass sich mit steigender Anzahl an Iterationen des wechselseitigen Informationsaustausches, die Knotenrepräsentationen im vektoriellen Raum angleichen und somit nicht mehr unterschieden werden können. In dieser Forschungsarbeit wird eine effiziente Methode vorgestellt, die die klassische GNN Architektur aufbricht und eine Vermittlerschicht in den herkömmlichen Verarbeitungsfluss einarbeitet. Konkret gesprochen werden hierbei Knotenrepräsentationen an ausgezeichnete Experten geschickt. Jeder Experte verarbeitet auf idiosynkratischer Basis die Knoteninformation. Ausgehend von einem Anfrageknoten liegt das Kriterium für die Unterscheidbarkeit von Experten in der restriktiven Verarbeitung lokaler Information. Diese neue Heuristik wird als 'Graph Shell Attention' (SEA) bezeichnet und beschreibt die Informationsverarbeitung unterschiedlicher Teilgraphen von Experten unter der Verwendung der Transformer-technologie. Eine zuverlässige Weiterleitung von Informationen über größere Kommunikationsnetzwerken, sozialen Netzwerken oder Sensorennetzwerken spielen eine wichtige Rolle in Anwendungen der Marktanalyse, der Analyse eines sozialen Gefüges, oder der Überwachung der physischen und umweltorientierten Bedingungen. Innerhalb dieser Anwendungen können Fälle auftreten, wo Freundschaftsbeziehungen nicht mehr aktuell sind, wo die Kommunikation zweier Endpunkte zusammenbricht, welches mittels einer Unsicherheit des Informationsaustausches zweier Endpunkte ausgedrückt werden kann. Diese Arbeit untersucht die Optimierung des Informationsflusses in Netzwerken, deren Verbindungen unsicher sind, hinsichtlich der Bedingung, dass nur ein Bruchteil der möglichen Kanten für den Informationsaustausch benutzt werden dürfen. Eine eigens entwickelte Datenstruktur - der F-Baum - wird eingeführt, die 2 NP-harte Teilprobleme auf einmal adressiert: zum einen die Berechnung des erwartbaren Informationsflusses und zum anderen die Auswahl der optimalen Kanten. Der F-Baum unterscheidet hierbei unabhängige Zusammenhangskomponenten der wahrscheinlichkeitsbasierten Eingabedaten, deren Informationsfluss entweder analytisch korrekt und effizient berechnet werden können, oder lokal über traditionelle Monte-Carlo sampling approximiert werden können. Der darauffolgende Abschnitt dieser Arbeit befasst sich mit einem Graphproblem aus Sicht der Optimierungsforschung angewandter Mathematik. Es wird eine neue Variante der Tourenplanung vorgestellt, welches neben kundenspezifischer Zeitfenster auch flexible Zustellstandorte beinhaltet. Darüber hinaus obliegt den Zielorten, an denen Kunden bedient werden können, weiteren Kapazitätslimitierungen. Aus praktischer Sicht ist das VRPTW-FL (engl.: "Vehicle Routing Problem with Time Windows and Flexible Locations") eine bedeutende Problemstellung für Paketdienstleister, Routenplanung mit eingeschränkten Stellplätzen oder auch für die praktische Planung der Arbeitsaufteilung von behandelnden Therapeuten/-innen und Ärzten/-innen in einem Krankenhaus. In dieser Arbeit wird für die Bewältigung dieser Problemstellung eine Metaheuristik vorgestellt, die einen hybriden Ansatz mit der sogenannten Adaptive Large Neighborhood Search (ALNS) impliziert. Darüber hinaus wird als Konstruktionsheuristik ein 'Backtracking'-Mechanismus (dt.: Rückverfolgung) angewandt, um initiale Startlösungen aus dem Lösungssuchraum auszuschließen, die weniger vielversprechend sind. In der Evaluierung dieses neuen Ansatz werden Krankenhausdaten untersucht, um auch die Nützlichkeit von flexiblen Zielorten unter verschiedenen Kostenfunktionen herauszuarbeiten. Im letzten Kapitel dieser Dissertation werden Trends in sozialen Daten analysiert, die Auskunft über die Stimmung der Benutzer liefern, sowie Einblicke in tagesaktuelle Geschehnisse gewähren. Ein Kennzeichen solcher Trends liegt in dem Aufbraußen von inhaltsspezifischen Themen innerhalb eines Zeitfensters, die von der durchschnittlichen Erscheinungshäufigkeit desselben Themas signifikant abweichen. Die Untersuchung der Verbreitung solches Trends über die zeitliche und örtliche Dimension erlaubt es, Trends in Archetypen zu klassifizieren, um somit die Ausbreitung zukünftiger Trends hervorzusagen. Mit der immerwährenden Skalierung von Graphdaten und deren Komplexität, und den Fortschritten innerhalb der künstlichen Intelligenz, wird das maschinelle Lernen unweigerlich weiterhin eine wesentliche Rolle spielen, um Graphdaten zu modellieren, analysieren und schlussendlich die Wissensextraktion aus derartigen Daten maßgeblich zu fördern.La théorie des graphes s'est révélée être une langue universel pour décrire les systèmes complexes modernes. L'élégant cadre théorique des graphes a attiré l'attention des chercheurs pendant des décennies. Par conséquent, les graphes sont devenus une structure de données omniprésente dans diverses applications où une caractéristique relationnelle est évidente. Les applications basées sur les graphes se retrouvent, par exemple, dans l'analyse des réseaux sociaux, les réseaux de télécommunication, les processus logistiques, les systèmes de recommandation, la modélisation des interactions cinétiques dans les réseaux de protéines, ou l'"Internet des objets" (IoT) où la modélisation de milliards de dispositifs interconnectés basés sur le web est d'une importance capitale. Cette thèse se penche sur les défis posés par les applications modernes des graphes. Elle propose un modèle de regroupement spectral robuste et accéléré dans les graphes homogènes et de nouveaux modèles d'enveloppe de graphe pilotés par transformateur pour les graphes attribués. Une nouvelle structure de données est introduite pour les graphes probabilistes afin de calculer efficacement le flux d'informations. De plus, un algorithme métaheuristique est conçu pour trouver une bonne solution à un problème d'optimisation composé d'un problème étendu de routage de véhicules. La thèse se termine par une analyse des flux de tendances dans les données des médias sociaux. La détection de communautés au sein d'un graphe est une tâche fondamentale d'exploration de données qui présente un intérêt dans pratiquement tous les domaines et sert également d'étape de prétraitement non supervisé pour de nombreuses tâches en aval. L'une des méthodes de regroupement les mieux établies est le regroupement spectral. Cependant, le regroupement spectral standard est très sensible aux données d'entrée bruitées, et l'eigendecomposition a une complexité d'exécution cubique élevée O(n^3). S'attaquer à l'un de ces problèmes exacerbe souvent l'autre. Cette thèse présente un nouveau modèle qui accélère l'étape d'eigendecomposition en la remplaçant par une approximation de Nyström. La robustesse est obtenue en séparant itérativement les données en une partie nettoyée et une partie bruyante. Dans ce processus, la représentation des données d'entrée sous forme de graphe est essentielle pour identifier les parties des données qui sont bien connectées en analysant les distances des sommets dans l'espace propre. Avec les progrès des architectures de Deep Learning, nous observons également une poussée de la recherche sur l'apprentissage de la représentation graphique. Le paradigme du passage de messages dans les réseaux neuronaux graphiques (GNN) formalise une heuristique prédominante pour les données graphiques multi-relationnelles et attribuées afin d'apprendre les représentations des nœuds. Dans les applications en aval, nous pouvons utiliser les représentations pour résoudre des problèmes théoriques tels que la classification des nœuds, la classification/régression des graphes et la prédiction des relations. Cependant, un problème courant dans les GNN est connu sous le nom de lissage excessif. En augmentant le nombre d'itérations dans le passage de messages, les représentations des nœuds du graphe d'entrée s'alignent et deviennent indiscernables. Cette thèse montre un moyen efficace d'assouplir l'architecture GNN en employant une heuristique de routage dans le flux de travail général. Plus précisément, une couche supplémentaire achemine les représentations des nœuds vers des experts spécialisés. Chaque expert calcule les représentations en fonction de son flux de travail GNN respectif. Les définitions de GNN distincts résultent de k vues localisées à partir d'un nœud central. Cette procédure est appelée Graph Shell Attention (SEA), dans laquelle les experts traitent différents sous-graphes à l'aide d'un transformateur. La propagation fiable d'informations par le biais de grands réseaux de communication, de réseaux sociaux ou de réseaux de capteurs est importante pour les applications concernant le marketing, l'analyse sociale ou la surveillance des conditions physiques ou environnementales. Cependant, les liens sociaux d'amitié peuvent être obsolètes, et les liens de communication peuvent échouer, induisant la notion d'incertitude dans de tels réseaux. Cette thèse aborde le problème de l'optimisation de la propagation de l'information dans les réseaux incertains compte tenu d'un budget contraint d'arêtes. Une structure de données spécialisée, appelée F-tree, traite deux sous-problèmes NP-hard: le calcul du flux d'information attendu et le choix optimal des arêtes. L'arbre F identifie les composants indépendants d'un graphe d'entrée probabiliste pour lesquels le flux d'informations peut être calculé analytiquement et efficacement ou pour lesquels l'échantillonnage Monte-Carlo traditionnel peut être appliqué indépendamment du reste du réseau. La partie suivante de la thèse couvre un problème de graphe du point de vue de la recherche opérationnelle. Une nouvelle variante du célèbre problème d'acheminement par véhicule (VRP) est introduite, où les clients sont servis dans une fenêtre temporelle spécifique (TW), ainsi que des lieux de livraison flexibles (FL) incluant des contraintes de capacité. Ces dernières impliquent que chaque client est programmé dans l'un des emplacements de service de livraison à capacité. En pratique, le problème VRPTW-FL est pertinent pour des applications de livraison de colis, d'acheminement avec un espace de stationnement limité ou, par exemple, dans le cadre de la programmation de kinésithérapeutes à l'échelle d'un hôpital. Cette thèse présente une métaheuristique construite sur une recherche hybride de grands voisinages adaptatifs (ALNS). En outre, un mécanisme de retour en arrière dans la phase de construction est introduit pour modifier les décisions insatisfaisantes à des stades précoces. Dans l'étude computationnelle, des données hospitalières sont utilisées pour évaluer l'utilité de lieux de livraison flexibles et de diverses fonctions de coût. Dans la dernière partie de la thèse, les tendances des médias sociaux sont analysées, ce qui donne un aperçu du sentiment des utilisateurs et des sujets d'actualité. Ces tendances consistent en des rafales de messages concernant un sujet particulier dans un laps de temps donné, s'écartant de manière significative de la fréquence moyenne d'apparition du même sujet. Cette thèse présente une méthode de classification des archétypes de tendances afin de prédire leur diffusion future en étudiant la diffusion de ces tendances dans l'espace et dans le temps. D'une manière générale, avec l'augmentation constante de l'échelle et de la complexité des ensembles de données structurées en graphe et les progrès de l'intelligence artificielle, les modèles soutenus par l'IA joueront inévitablement un rôle important dans l'analyse, la modélisation et l'amélioration de l'extraction de connaissances à partir de données en graphe

Data-Driven Representation Learning in Multimodal Feature Fusion

abstract: Modern machine learning systems leverage data and features from multiple modalities to gain more predictive power. In most scenarios, the modalities are vastly different and the acquired data are heterogeneous in nature. Consequently, building highly effective fusion algorithms is at the core to achieve improved model robustness and inferencing performance. This dissertation focuses on the representation learning approaches as the fusion strategy. Specifically, the objective is to learn the shared latent representation which jointly exploit the structural information encoded in all modalities, such that a straightforward learning model can be adopted to obtain the prediction. We first consider sensor fusion, a typical multimodal fusion problem critical to building a pervasive computing platform. A systematic fusion technique is described to support both multiple sensors and descriptors for activity recognition. Targeted to learn the optimal combination of kernels, Multiple Kernel Learning (MKL) algorithms have been successfully applied to numerous fusion problems in computer vision etc. Utilizing the MKL formulation, next we describe an auto-context algorithm for learning image context via the fusion with low-level descriptors. Furthermore, a principled fusion algorithm using deep learning to optimize kernel machines is developed. By bridging deep architectures with kernel optimization, this approach leverages the benefits of both paradigms and is applied to a wide variety of fusion problems. In many real-world applications, the modalities exhibit highly specific data structures, such as time sequences and graphs, and consequently, special design of the learning architecture is needed. In order to improve the temporal modeling for multivariate sequences, we developed two architectures centered around attention models. A novel clinical time series analysis model is proposed for several critical problems in healthcare. Another model coupled with triplet ranking loss as metric learning framework is described to better solve speaker diarization. Compared to state-of-the-art recurrent networks, these attention-based multivariate analysis tools achieve improved performance while having a lower computational complexity. Finally, in order to perform community detection on multilayer graphs, a fusion algorithm is described to derive node embedding from word embedding techniques and also exploit the complementary relational information contained in each layer of the graph.Dissertation/ThesisDoctoral Dissertation Electrical Engineering 201

Exploration and visualization of design spaces with applications to negative stiffness metamaterials

Engineering design problems are commonly hierarchical and multilevel which requires coordination between models at each scale. If the models are computationally expensive or highly nonlinear, such as many materials design applications, identification of an optimal design may be exceptionally difficult. Alternatives to optimization-based methods include set-based methods that classify and track sets or ensembles of high performance designs. By relaxing the requirement for an optimal design, it is often possible to identify promising, high performance regions of the design space efficiently. Bayesian network classifiers (BNCs) are such an approach that can identify these regions of promising designs in the presence of nonlinear relationships and mixed variables. When manufacturing the promising designs identified by the BNC approach, the intended design may not match the physical embodiment due to manufacturing variations. These variations may alter the performance of the design leading to unsatisfactory results and products. To facilitate selection of not only high performance but reliably manufacturable designs, a method for incorporating manufacturing variation, modeled as a joint probability distribution is presented for the BNC approach. The approach utilizes a dual classification strategy that identifies regions of design that are likely to perform well within statistical confidence. These design regions can be high dimensional in which it becomes very difficult to identify and visualize clusters of promising designs. This leads to a lack of understanding of the design space. To enhance the designer’s knowledge of the design space, this work presents a method, based on spectral clustering, that can identify high performance regions in a high dimensional space. Furthermore, a method for visualizing each individual design region is presented that is accomplished by incorporating t-Distributed Stochastic Neighbor Embedding. Through the accomplishment of these three tasks—incorporating manufacturing variation, clustering, and visualizing—a novel design methodology will be developed which will then be applied to identify satisfactory designs for a negative stiffness metamaterials design problem which will be manufactured and tested.Mechanical Engineerin

Multi-view Subspace Learning for Large-Scale Multi-Modal Data Analysis

Dimensionality reduction methods play a big role within the modern machine learning techniques, and subspace learning is one of the common approaches to it. Although various methods have been proposed over the past years, many of them suffer from limitations related to the unimodality assumptions on the data and low speed in the cases of high-dimensional data (in linear formulations) or large datasets (in kernel-based formulations). In this work, several methods for overcoming these limitations are proposed. In this thesis, the problem of the large-scale multi-modal data analysis for single- and multi-view data is discussed, and several extensions for Subclass Discriminant Analysis (SDA) are proposed. First, a Spectral Regression Subclass Discriminant Analysis method relying on the Graph Embedding-based formulation of SDA is proposed as a way to reduce the training time, and it is shown how the solution can be obtained efficiently, therefore reducing the computational requirements. Secondly, a novel multi-view formulation for Subclass Discriminant Analysis is proposed, allowing to extend it to data coming from multiple views. Besides, a speed-up approach for the multi-view formulation that allows reducing the computational requirements of the method is proposed. Linear and nonlinear kernel-based formulations are proposed for all the extensions. Experiments are performed on nine single-view and nine multi-view datasets and the accuracy and speed of the proposed extensions are evaluated. Experimentally it is shown that the proposed approaches result in a significant reduction of the training time while providing competitive performance, as compared to other subspace-learning based methods

Hierarchical spectral clustering reveals brain size and shape changes in asymptomatic carriers of C9orf72

Supplementary data: fcac182_Supplementary_Data - https://oup.silverchair-cdn.com/oup/backfile/Content_public/Journal/braincomms/4/4/10.1093_braincomms_fcac182/1/fcac182_supplementary_data.pdf?Expires=1665138780&Signature=oJFozMlNZiAmxd4~XZaq7YKd7waxislas45NEOp9AiZv-fUYr7X~LhZxFgvYXpCVINyQUQrXe0pgrm9L5kv7xdb0LltVuoEOjwb5uVveMyHMfuqTdCBsEzTVZidx9GuuOB79JsHNYHkUZPsXLiU8-lrosrTb3tasr8Mpv31u7ZVZT~4uGdUf06UsIRu7AEn4bfKf64iwudmFr1QyrLJkXMZm0uJ4e5kh8f7k6Xm~rZGqkaiphsQ~Oat4JHssfuCe5Wibgc4m~rMjQeOmutR3R7KicfH4j3xuab1mzCbf-H~~Ed5Yt8mtlMTsyDB3t-8z3dNVaS2aBrwCABvfa3G2yg__&Key-Pair-Id=APKAIE5G5CRDK6RD3PGA (pdf file).GENFI consortium authors Sónia Afonso, Maria Rosario Almeida, Sarah Anderl-Straub, Christin Andersson, Anna Antonell, Silvana Archetti, Andrea Arighi, Mircea Balasa, Myriam Barandiaran, Nuria Bargalló, Robart Bartha, Benjamin Bender, Alberto Benussi, Sandra Black, Martina Bocchetta, Sergi Borrego-Ecija, Jose Bras, Marta Canada, Valentina Cantoni, Paola Caroppo, David Cash, Miguel Castelo-Branco, Rhian Convery, Thomas Cope, Giuseppe Di Fede, Alina Díez, Diana Duro, Chiara Fenoglio, Catarina B. Ferreira, Nick Fox, Morris Freedman, Giorgio Fumagalli, Alazne Gabilondo, Roberto Gasparotti, Serge Gauthier, Stefano Gazzina, Giorgio Giaccone, Ana Gorostidi, Caroline Greaves, Rita Guerreiro, Carolin Heller, Tobias Hoegen, Begoña Indakoetxea, Vesna Jelic, Lize Jiskoot, Hans-Otto Karnath, Ron Keren, Tobias Langheinrich, Maria João Leitão, Albert Lladó, Sandra Loosli, Carolina Maruta, Simon Mead, Lieke Meeter, Gabriel Miltenberger, Rick van Minkelen, Sara Mitchell, Katrina Moore, Jennifer Nicholas, Linn Öijerstedt, Jaume Olives, Sebastien Ourselin, Alessandro Padovani, Jessica Panman, Janne M. Papma, Georgia Peakman, Yolande Pijnenburg, Enrico Premi, Sara Prioni, Catharina Prix, Rosa Rademakers, Veronica Redaelli, Tim Rittman, Ekaterina Rogaeva, Pedro Rosa-Neto, Giacomina Rossi, Mar tin Rossor, Beatriz Santiago, Elio Scarpini, Sonja Schönecker, Elisa Semler, Rachelle Shafei, Christen Shoesmith, Miguel Tábuas-Pereira, Mikel Tainta, Ricardo Taipa, David Tang-Wai, David L Thomas, Paul Thompson, Hakan Thonberg, Carolyn Timberlake, Pietro Tiraboschi, Emily Todd, Michele Veldsman, Ana Verdelho, Jorge Villanua, Jason Warren, Carlo Wilke, Ione Woollacott, Elisabeth Wlasich, Henrik Zetterberg, Miren ZulaicaCopyright © The Author(s) 2022. Traditional methods for detecting asymptomatic brain changes in neurodegenerative diseases such as Alzheimer’s disease or frontotemporal degeneration typically evaluate changes in volume at a predefined level of granularity, e.g. voxel-wise or in a priori defined cortical volumes of interest. Here, we apply a method based on hierarchical spectral clustering, a graph-based partitioning technique. Our method uses multiple levels of segmentation for detecting changes in a data-driven, unbiased, comprehensive manner within a standard statistical framework. Furthermore, spectral clustering allows for detection of changes in shape along with changes in size. We performed tensor-based morphometry to detect changes in the Genetic Frontotemporal dementia Initiative asymptomatic and symptomatic frontotemporal degeneration mutation carriers using hierarchical spectral clustering and compared the outcome to that obtained with a more conventional voxel-wise tensor- and voxel-based morphometric analysis. In the symptomatic groups, the hierarchical spectral clustering-based method yielded results that were largely in line with those obtained with the voxel-wise approach. In asymptomatic C9orf72 expansion carriers, spectral clustering detected changes in size in medial temporal cortex that voxel-wise methods could only detect in the symptomatic phase. Furthermore, in the asymptomatic and the symptomatic phases, the spectral clustering approach detected changes in shape in the premotor cortex in C9orf72. In summary, the present study shows the merit of hierarchical spectral clustering for data-driven segmentation and detection of structural changes in the symptomatic and asymptomatic stages of monogenic frontotemporal degeneration.KU Leuven’s ‘Mady Browaeys Fonds voor Onderzoek naar Frontotemporale Degeneratie’