Put three and three together: Triangle-driven community detection

Community detection has arisen as one of the most relevant topics in the field of graph data mining due to its applications in many fields such as biology, social networks, or network traffic analysis. Although the existing metrics used to quantify the quality of a community work well in general, under some circumstances, they fail at correctly capturing such notion. The main reason is that these metrics consider the internal community edges as a set, but ignore how these actually connect the vertices of the community. We propose the Weighted Community Clustering (WCC), which is a new community metric that takes the triangle instead of the edge as the minimal structural motif indicating the presence of a strong relation in a graph. We theoretically analyse WCC in depth and formally prove, by means of a set of properties, that the maximization of WCC guarantees communities with cohesion and structure. In addition, we propose Scalable Community Detection (SCD), a community detection algorithm based on WCC, which is designed to be fast and scalable on SMP machines, showing experimentally that WCC correctly captures the concept of community in social networks using real datasets. Finally, using ground-truth data, we show that SCD provides better quality than the best disjoint community detection algorithms of the state of the art while performing faster.Peer ReviewedPostprint (author's final draft

Business process model repositories : efficient process retrieval

As organizations increasingly work in process-oriented manner, the number of business process models that they develop and have to maintain increases. As a consequence, it has become common for organizations to have collections of hundreds or even thousands of business process models. When a collection contains such a large number of business process models, it is impossible to manage that collection manually. Therefore, Business Process (BP) Model Repositories are required that store large collections of process models and provide techniques for managing these collections automatically and efficiently. The goal of research described in this thesis is to improve on existing BP Model Repositories, by improving the management techniques that are supported by these repositories on an aspect that has received little attention so far. Looking ahead at the results of the research, the aspect that will be selected for improvement is the process retrieval aspect. The two main research activities that will be carried in the context of this research are the following. Firstly, a survey of Business Process Model Repositories is performed to identity an unsolved aspect to be enhanced. The functionality of existing BP Model Repositories is listed and summarized as a framework for BP Model Repositories. After comparing the functionality that is provided by existing BP Model Repositories, based on the framework, efficient process retrieval is selected as the aspect that will be improved. This aspect is selected, because, although existing BP Model Repositories provide techniques for process retrieval, none of them focus on the efficiency of process retrieval. Secondly, an indexing technique for process retrieval (both process similarity search and process querying) is proposed. The index is constructed using features of process models. Features are small and characteristic fragments of process models. As such, by matching features of a given query/search model and features of a process model in a collection, a small set of models in the collection that potentially match the query/search model can be retrieved efficiently through the index. Techniques are also proposed to further check whether a potential match is an actual match for the query/search model. All of the above techniques are implemented as a component of the AProMoRe (an Advanced Process Model Repository) process repository. To evaluate the proposed process retrieval techniques, experiments are run using both real-life and synthetic process model collections. Experimental results show that on average the process retrieval techniques proposed in this thesis performs at least one order of magnitude faster than existing techniques

Network partitioning algorithms as cooperative games

International audienceThe paper is devoted to game-theoretic methods for community detection in networks. The traditional methods for detecting community structure are based on selecting dense subgraphs inside the network. Here we propose to use the methods of cooperative game theory that highlight not only the link density but also the mechanisms of cluster formation. Specifically, we suggest two approaches from cooperative game theory: the first approach is based on the Myerson value, whereas the second approach is based on hedonic games. Both approaches allow to detect clusters with various resolutions. However, the tuning of the resolution parameter in the hedonic games approach is particularly intuitive. Furthermore, the modularity-based approach and its generalizations as well as ratio cut and normalized cut methods can be viewed as particular cases of the hedonic games. Finally, for approaches based on potential hedonic games we suggest a very efficient computational scheme using Gibbs sampling

Graph-Based Approaches to Protein StructureComparison - From Local to Global Similarity

The comparative analysis of protein structure data is a central aspect of structural bioinformatics. Drawing upon structural information allows the inference of function for unknown proteins even in cases where no apparent homology can be found on the sequence level. Regarding the function of an enzyme, the overall fold topology might less important than the specific structural conformation of the catalytic site or the surface region of a protein, where the interaction with other molecules, such as binding partners, substrates and ligands occurs. Thus, a comparison of these regions is especially interesting for functional inference, since structural constraints imposed by the demands of the catalyzed biochemical function make them more likely to exhibit structural similarity. Moreover, the comparative analysis of protein binding sites is of special interest in pharmaceutical chemistry, in order to predict cross-reactivities and gain a deeper understanding of the catalysis mechanism. From an algorithmic point of view, the comparison of structured data, or, more generally, complex objects, can be attempted based on different methodological principles. Global methods aim at comparing structures as a whole, while local methods transfer the problem to multiple comparisons of local substructures. In the context of protein structure analysis, it is not a priori clear, which strategy is more suitable. In this thesis, several conceptually different algorithmic approaches have been developed, based on local, global and semi-global strategies, for the task of comparing protein structure data, more specifically protein binding pockets. The use of graphs for the modeling of protein structure data has a long standing tradition in structural bioinformatics. Recently, graphs have been used to model the geometric constraints of protein binding sites. The algorithms developed in this thesis are based on this modeling concept, hence, from a computer scientist's point of view, they can also be regarded as global, local and semi-global approaches to graph comparison. The developed algorithms were mainly designed on the premise to allow for a more approximate comparison of protein binding sites, in order to account for the molecular flexibility of the protein structures. A main motivation was to allow for the detection of more remote similarities, which are not apparent by using more rigid methods. Subsequently, the developed approaches were applied to different problems typically encountered in the field of structural bioinformatics in order to assess and compare their performance and suitability for different problems. Each of the approaches developed during this work was capable of improving upon the performance of existing methods in the field. Another major aspect in the experiments was the question, which methodological concept, local, global or a combination of both, offers the most benefits for the specific task of protein binding site comparison, a question that is addressed throughout this thesis

Algorithms and Software for the Analysis of Large Complex Networks

The work presented intersects three main areas, namely graph algorithmics, network science and applied software engineering. Each computational method discussed relates to one of the main tasks of data analysis: to extract structural features from network data, such as methods for community detection; or to transform network data, such as methods to sparsify a network and reduce its size while keeping essential properties; or to realistically model networks through generative models

In silico strategies to study polypharmacology of G-protein-coupled receptors

The development of drugs that simultaneously target multiple receptors in a rational way (i.e., 'magic shotguns') is regarded as a promising approach for drug discovery to treat complex, multi-factorial and multi-pathogenic diseases. My major goal is to develop and employ different computational approaches towards the rational design of drugs with selective polypharmacology towards guanine nucleotide-binding protein (G-protein)-coupled receptors (GPCRs) to treat central nervous system diseases. Our methodologies rely on the advances in chemocentric informatics and chemogenomics to generate experimentally testable hypotheses that are derived by fusing independent lines of evidence. We posit that such hypothesis fusion approach allows us to improve the overall success rates of in silico lead identification efforts. We have developed an integrated computational approach that combines Quantitative Structure-Activity Relationships (QSAR) modeling, model-based virtual screening (VS), gene expression analysis and mining of the biological literature for drug discovery. The dissertation research described herein is focused on: (1) The development of robust data-driven Quantitative Structure-Activity Relationship (QSAR) models of single target GPCR datasets that will amount to the compendium of GPCR predictors: the GPCR QSARome; (2) The development of robust data-driven QSAR models for families of GPCRs and other trans-membrane molecular targets (i.e., sigma receptors) and the application of models as virtual screening tools for the quick prioritization of compounds for biological testing across receptor families; (3) The development of novel integrative chemocentric informatics approaches to predict receptor-mediated clinical effects of chemicals. Results indicated that our computational efforts to establish a compendium of computational predictors and devise an integrative chemocentric informatics approach to study polypharmacology in silico will eventually lead to useful and reliable tools aimed at identifying and enriching chemical libraries with compounds that have the desired activities for more than one molecular target of interest

A lightweight, graph-theoretic model of class-based similarity to support object-oriented code reuse.

The work presented in this thesis is principally concerned with the development of a method and set of tools designed to support the identification of class-based similarity in collections of object-oriented code. Attention is focused on enhancing the potential for software reuse in situations where a reuse process is either absent or informal, and the characteristics of the organisation are unsuitable, or resources unavailable, to promote and sustain a systematic approach to reuse. The approach builds on the definition of a formal, attributed, relational model that captures the inherent structure of class-based, object-oriented code. Based on code-level analysis, it relies solely on the structural characteristics of the code and the peculiarly object-oriented features of the class as an organising principle: classes, those entities comprising a class, and the intra and inter-class relationships existing between them, are significant factors in defining a two-phase similarity measure as a basis for the comparison process. Established graph-theoretic techniques are adapted and applied via this model to the problem of determining similarity between classes. This thesis illustrates a successful transfer of techniques from the domains of molecular chemistry and computer vision. Both domains provide an existing template for the analysis and comparison of structures as graphs. The inspiration for representing classes as attributed relational graphs, and the application of graph-theoretic techniques and algorithms to their comparison, arose out of a well-founded intuition that a common basis in graph-theory was sufficient to enable a reasonable transfer of these techniques to the problem of determining similarity in object-oriented code. The practical application of this work relates to the identification and indexing of instances of recurring, class-based, common structure present in established and evolving collections of object-oriented code. A classification so generated additionally provides a framework for class-based matching over an existing code-base, both from the perspective of newly introduced classes, and search "templates" provided by those incomplete, iteratively constructed and refined classes associated with current and on-going development. The tools and techniques developed here provide support for enabling and improving shared awareness of reuse opportunity, based on analysing structural similarity in past and ongoing development, tools and techniques that can in turn be seen as part of a process of domain analysis, capable of stimulating the evolution of a systematic reuse ethic

Computational approaches to virtual screening in human central nervous system therapeutic targets

In the past several years of drug design, advanced high-throughput synthetic and analytical chemical technologies are continuously producing a large number of compounds. These large collections of chemical structures have resulted in many public and commercial molecular databases. Thus, the availability of larger data sets provided the opportunity for developing new knowledge mining or virtual screening (VS) methods. Therefore, this research work is motivated by the fact that one of the main interests in the modern drug discovery process is the development of new methods to predict compounds with large therapeutic profiles (multi-targeting activity), which is essential for the discovery of novel drug candidates against complex multifactorial diseases like central nervous system (CNS) disorders. This work aims to advance VS approaches by providing a deeper understanding of the relationship between chemical structure and pharmacological properties and design new fast and robust tools for drug designing against different targets/pathways. To accomplish the defined goals, the first challenge is dealing with big data set of diverse molecular structures to derive a correlation between structures and activity. However, an extendable and a customizable fully automated in-silico Quantitative-Structure Activity Relationship (QSAR) modeling framework was developed in the first phase of this work. QSAR models are computationally fast and powerful tool to screen huge databases of compounds to determine the biological properties of chemical molecules based on their chemical structure. The generated framework reliably implemented a full QSAR modeling pipeline from data preparation to model building and validation. The main distinctive features of the designed framework include a)efficient data curation b) prior estimation of data modelability and, c)an-optimized variable selection methodology that was able to identify the most biologically relevant features responsible for compound activity. Since the underlying principle in QSAR modeling is the assumption that the structures of molecules are mainly responsible for their pharmacological activity, the accuracy of different structural representation approaches to decode molecular structural information largely influence model predictability. However, to find the best approach in QSAR modeling, a comparative analysis of two main categories of molecular representations that included descriptor-based (vector space) and distance-based (metric space) methods was carried out. Results obtained from five QSAR data sets showed that distance-based method was superior to capture the more relevant structural elements for the accurate characterization of molecular properties in highly diverse data sets (remote chemical space regions). This finding further assisted to the development of a novel tool for molecular space visualization to increase the understanding of structure-activity relationships (SAR) in drug discovery projects by exploring the diversity of large heterogeneous chemical data. In the proposed visual approach, four nonlinear DR methods were tested to represent molecules lower dimensionality (2D projected space) on which a non-parametric 2D kernel density estimation (KDE) was applied to map the most likely activity regions (activity surfaces). The analysis of the produced probabilistic surface of molecular activities (PSMAs) from the four datasets showed that these maps have both descriptive and predictive power, thus can be used as a spatial classification model, a tool to perform VS using only structural similarity of molecules. The above QSAR modeling approach was complemented with molecular docking, an approach that predicts the best mode of drug-target interaction. Both approaches were integrated to develop a rational and re-usable polypharmacology-based VS pipeline with improved hits identification rate. For the validation of the developed pipeline, a dual-targeting drug designing model against Parkinson’s disease (PD) was derived to identify novel inhibitors for improving the motor functions of PD patients by enhancing the bioavailability of dopamine and avoiding neurotoxicity. The proposed approach can easily be extended to more complex multi-targeting disease models containing several targets and anti/offtargets to achieve increased efficacy and reduced toxicity in multifactorial diseases like CNS disorders and cancer. This thesis addresses several issues of cheminformatics methods (e.g., molecular structures representation, machine learning, and molecular similarity analysis) to improve and design new computational approaches used in chemical data mining. Moreover, an integrative drug-designing pipeline is designed to improve polypharmacology-based VS approach. This presented methodology can identify the most promising multi-targeting candidates for experimental validation of drug-targets network at the systems biology level in the drug discovery process

A probabilistic model for the evaluation of module extraction algorithms in complex biological networks

This thesis presents CiGRAM, a model of complex networks ith known modular structure that is capable of generating realistic graph topology. Much of the recent focus on module detection has been geared towards developing new algorithms capable of detecting biologically significant clusters. However, evaluating clusterings detected by different methods shows that there is little topological agreement or consensus in terms of meta-data despite most methods discovering modules with significant ontology. In this thesis an approach to modelling complex networks with ground-truth modular structure is presented. This approach is capable of generating graphs with heterogeneous degree distributions, high clustering coefficients and assortative degree correlations observed in real data but often ignored in existing benchmarks. Moreover, the model for modular structure concludes that non-modular random graphs are indistinguishable from modules. This model can be tuned to fit many empirical biological and non-biological datasets through fitting target graph summary statistics. The ground-truth structure allows the evaluation of module extraction algorithms in a domain specific context. Furthermore, it was found that degree assortativity appears to negatively impact several module extraction methods such as the popular infomap and modularity maximisation methods. Results presented disagree with other benchmark models highlighting the potential for future research into improving existing methods in ways that challenge assumptions about the detectability of modules

Metadata-driven data integration

Cotutela: Universitat Politècnica de Catalunya i Université Libre de Bruxelles, IT4BI-DC programme for the joint Ph.D. degree in computer science.Data has an undoubtable impact on society. Storing and processing large amounts of available data is currently one of the key success factors for an organization. Nonetheless, we are recently witnessing a change represented by huge and heterogeneous amounts of data. Indeed, 90% of the data in the world has been generated in the last two years. Thus, in order to carry on these data exploitation tasks, organizations must first perform data integration combining data from multiple sources to yield a unified view over them. Yet, the integration of massive and heterogeneous amounts of data requires revisiting the traditional integration assumptions to cope with the new requirements posed by such data-intensive settings. This PhD thesis aims to provide a novel framework for data integration in the context of data-intensive ecosystems, which entails dealing with vast amounts of heterogeneous data, from multiple sources and in their original format. To this end, we advocate for an integration process consisting of sequential activities governed by a semantic layer, implemented via a shared repository of metadata. From an stewardship perspective, this activities are the deployment of a data integration architecture, followed by the population of such shared metadata. From a data consumption perspective, the activities are virtual and materialized data integration, the former an exploratory task and the latter a consolidation one. Following the proposed framework, we focus on providing contributions to each of the four activities. We begin proposing a software reference architecture for semantic-aware data-intensive systems. Such architecture serves as a blueprint to deploy a stack of systems, its core being the metadata repository. Next, we propose a graph-based metadata model as formalism for metadata management. We focus on supporting schema and data source evolution, a predominant factor on the heterogeneous sources at hand. For virtual integration, we propose query rewriting algorithms that rely on the previously proposed metadata model. We additionally consider semantic heterogeneities in the data sources, which the proposed algorithms are capable of automatically resolving. Finally, the thesis focuses on the materialized integration activity, and to this end, proposes a method to select intermediate results to materialize in data-intensive flows. Overall, the results of this thesis serve as contribution to the field of data integration in contemporary data-intensive ecosystems.Les dades tenen un impacte indubtable en la societat. La capacitat d’emmagatzemar i processar grans quantitats de dades disponibles és avui en dia un dels factors claus per l’èxit d’una organització. No obstant, avui en dia estem presenciant un canvi representat per grans volums de dades heterogenis. En efecte, el 90% de les dades mundials han sigut generades en els últims dos anys. Per tal de dur a terme aquestes tasques d’explotació de dades, les organitzacions primer han de realitzar una integració de les dades, combinantles a partir de diferents fonts amb l’objectiu de tenir-ne una vista unificada d’elles. Per això, aquest fet requereix reconsiderar les assumpcions tradicionals en integració amb l’objectiu de lidiar amb els requisits imposats per aquests sistemes de tractament massiu de dades. Aquesta tesi doctoral té com a objectiu proporcional un nou marc de treball per a la integració de dades en el context de sistemes de tractament massiu de dades, el qual implica lidiar amb una gran quantitat de dades heterogènies, provinents de múltiples fonts i en el seu format original. Per això, proposem un procés d’integració compost d’una seqüència d’activitats governades per una capa semàntica, la qual és implementada a partir d’un repositori de metadades compartides. Des d’una perspectiva d’administració, aquestes activitats són el desplegament d’una arquitectura d’integració de dades, seguit per la inserció d’aquestes metadades compartides. Des d’una perspectiva de consum de dades, les activitats són la integració virtual i materialització de les dades, la primera sent una tasca exploratòria i la segona una de consolidació. Seguint el marc de treball proposat, ens centrem en proporcionar contribucions a cada una de les quatre activitats. La tesi inicia proposant una arquitectura de referència de software per a sistemes de tractament massiu de dades amb coneixement semàntic. Aquesta arquitectura serveix com a planell per a desplegar un conjunt de sistemes, sent el repositori de metadades al seu nucli. Posteriorment, proposem un model basat en grafs per a la gestió de metadades. Concretament, ens centrem en donar suport a l’evolució d’esquemes i fonts de dades, un dels factors predominants en les fonts de dades heterogènies considerades. Per a l’integració virtual, proposem algorismes de rescriptura de consultes que usen el model de metadades previament proposat. Com a afegitó, considerem heterogeneïtat semàntica en les fonts de dades, les quals els algorismes de rescriptura poden resoldre automàticament. Finalment, la tesi es centra en l’activitat d’integració materialitzada. Per això proposa un mètode per a seleccionar els resultats intermedis a materialitzar un fluxes de tractament intensiu de dades. En general, els resultats d’aquesta tesi serveixen com a contribució al camp d’integració de dades en els ecosistemes de tractament massiu de dades contemporanisLes données ont un impact indéniable sur la société. Le stockage et le traitement de grandes quantités de données disponibles constituent actuellement l’un des facteurs clés de succès d’une entreprise. Néanmoins, nous assistons récemment à un changement représenté par des quantités de données massives et hétérogènes. En effet, 90% des données dans le monde ont été générées au cours des deux dernières années. Ainsi, pour mener à bien ces tâches d’exploitation des données, les organisations doivent d’abord réaliser une intégration des données en combinant des données provenant de sources multiples pour obtenir une vue unifiée de ces dernières. Cependant, l’intégration de quantités de données massives et hétérogènes nécessite de revoir les hypothèses d’intégration traditionnelles afin de faire face aux nouvelles exigences posées par les systèmes de gestion de données massives. Cette thèse de doctorat a pour objectif de fournir un nouveau cadre pour l’intégration de données dans le contexte d’écosystèmes à forte intensité de données, ce qui implique de traiter de grandes quantités de données hétérogènes, provenant de sources multiples et dans leur format d’origine. À cette fin, nous préconisons un processus d’intégration constitué d’activités séquentielles régies par une couche sémantique, mise en oeuvre via un dépôt partagé de métadonnées. Du point de vue de la gestion, ces activités consistent à déployer une architecture d’intégration de données, suivies de la population de métadonnées partagées. Du point de vue de la consommation de données, les activités sont l’intégration de données virtuelle et matérialisée, la première étant une tâche exploratoire et la seconde, une tâche de consolidation. Conformément au cadre proposé, nous nous attachons à fournir des contributions à chacune des quatre activités. Nous commençons par proposer une architecture logicielle de référence pour les systèmes de gestion de données massives et à connaissance sémantique. Une telle architecture consiste en un schéma directeur pour le déploiement d’une pile de systèmes, le dépôt de métadonnées étant son composant principal. Ensuite, nous proposons un modèle de métadonnées basé sur des graphes comme formalisme pour la gestion des métadonnées. Nous mettons l’accent sur la prise en charge de l’évolution des schémas et des sources de données, facteur prédominant des sources hétérogènes sous-jacentes. Pour l’intégration virtuelle, nous proposons des algorithmes de réécriture de requêtes qui s’appuient sur le modèle de métadonnées proposé précédemment. Nous considérons en outre les hétérogénéités sémantiques dans les sources de données, que les algorithmes proposés sont capables de résoudre automatiquement. Enfin, la thèse se concentre sur l’activité d’intégration matérialisée et propose à cette fin une méthode de sélection de résultats intermédiaires à matérialiser dans des flux des données massives. Dans l’ensemble, les résultats de cette thèse constituent une contribution au domaine de l’intégration des données dans les écosystèmes contemporains de gestion de données massivesPostprint (published version