Structuring heterogeneous biological information using fuzzy clustering of k-partite graphs

<p>Abstract</p> <p>Background</p> <p>Extensive and automated data integration in bioinformatics facilitates the construction of large, complex biological networks. However, the challenge lies in the interpretation of these networks. While most research focuses on the unipartite or bipartite case, we address the more general but common situation of <it>k</it>-partite graphs. These graphs contain <it>k </it>different node types and links are only allowed between nodes of different types. In order to reveal their structural organization and describe the contained information in a more coarse-grained fashion, we ask how to detect clusters within each node type.</p> <p>Results</p> <p>Since entities in biological networks regularly have more than one function and hence participate in more than one cluster, we developed a <it>k</it>-partite graph partitioning algorithm that allows for overlapping (fuzzy) clusters. It determines for each node a degree of membership to each cluster. Moreover, the algorithm estimates a weighted <it>k</it>-partite graph that connects the extracted clusters. Our method is fast and efficient, mimicking the multiplicative update rules commonly employed in algorithms for non-negative matrix factorization. It facilitates the decomposition of networks on a chosen scale and therefore allows for analysis and interpretation of structures on various resolution levels. Applying our algorithm to a tripartite disease-gene-protein complex network, we were able to structure this graph on a large scale into clusters that are functionally correlated and biologically meaningful. Locally, smaller clusters enabled reclassification or annotation of the clusters' elements. We exemplified this for the transcription factor MECP2.</p> <p>Conclusions</p> <p>In order to cope with the overwhelming amount of information available from biomedical literature, we need to tackle the challenge of finding structures in large networks with nodes of multiple types. To this end, we presented a novel fuzzy <it>k</it>-partite graph partitioning algorithm that allows the decomposition of these objects in a comprehensive fashion. We validated our approach both on artificial and real-world data. It is readily applicable to any further problem.</p

Elucidation of the Mechanism of Indonesian Traditional Medicine (Jamu) Based on Case Studies of Type 2 Diabetes Networks

Plant medicine is a kind of plant that can be used to solve various problems in the human body either due to illness or other disorders. Jamu is an Indonesian traditional medicine. It is essentially herbal medicine that made from natural materials taken from several parts of medicinal plants which contain some substances and compounds that important and beneficial for the body. So far, the efficacy for some type of jamu has been proven empirically. In this paper, to fill this gap, we intend to elucidate the mechanism of jamu using computational base approach. This research focus to a jamu for Type 2 Diabetes (T2D) which prescription consist of four plants: Ginger (Zingiber officinale), Bratawali (Tinospora crispa), Sembung (Blumea balsamifera), and Bitter Melon (Momordica charantia). The framework of analysis starts with generating the network with 3 components: active compounds, proteins target and gene ontology. After that, will implement clustering to those components using concept of tri-partite graphs fuzzy clustering. The main ingredients of 15 active compounds have high score probability which divided in different cluster by the pair of active compounds that have high synergic effect. T2D is not solely caused by protein abnormalities from insulin secretion (isoform insulin-degrading enzyme 1), but also caused by other proteins that involved in the inhibition of insulin in the pancreas. These proteins are Alpha-2C adrenergic receptors, beta-1 adrenergic receptor, and peroxisome proliferator-activated receptor delta, which have high probability in the same group

Knowledge-based matrix factorization temporally resolves the cellular responses to IL-6 stimulation

<p>Abstract</p> <p>Background</p> <p>External stimulations of cells by hormones, cytokines or growth factors activate signal transduction pathways that subsequently induce a re-arrangement of cellular gene expression. The analysis of such changes is complicated, as they consist of multi-layered temporal responses. While classical analyses based on clustering or gene set enrichment only partly reveal this information, matrix factorization techniques are well suited for a detailed temporal analysis. In signal processing, factorization techniques incorporating data properties like spatial and temporal correlation structure have shown to be robust and computationally efficient. However, such correlation-based methods have so far not be applied in bioinformatics, because large scale biological data rarely imply a natural order that allows the definition of a delayed correlation function.</p> <p>Results</p> <p>We therefore develop the concept of graph-decorrelation. We encode prior knowledge like transcriptional regulation, protein interactions or metabolic pathways in a weighted directed graph. By linking features along this underlying graph, we introduce a partial ordering of the features (e.g. genes) and are thus able to define a graph-delayed correlation function. Using this framework as constraint to the matrix factorization task allows us to set up the fast and robust graph-decorrelation algorithm (GraDe). To analyze alterations in the gene response in <it>IL-6 </it>stimulated primary mouse hepatocytes, we performed a time-course microarray experiment and applied GraDe. In contrast to standard techniques, the extracted time-resolved gene expression profiles showed that <it>IL-6 </it>activates genes involved in cell cycle progression and cell division. Genes linked to metabolic and apoptotic processes are down-regulated indicating that <it>IL-6 </it>mediated priming renders hepatocytes more responsive towards cell proliferation and reduces expenditures for the energy metabolism.</p> <p>Conclusions</p> <p>GraDe provides a novel framework for the decomposition of large-scale 'omics' data. We were able to show that including prior knowledge into the separation task leads to a much more structured and detailed separation of the time-dependent responses upon <it>IL-6 </it>stimulation compared to standard methods. A Matlab implementation of the GraDe algorithm is freely available at <url>http://cmb.helmholtz-muenchen.de/grade</url>.</p

Analysis and Visualisation of Edge Entanglement in Multiplex Networks

Cette thèse présente une nouvelle méthodologie pour analyser des réseaux. Nous développons l'intrication d'un réseau multiplex, qui se matérialise sous forme d'une mesure d'intensité et d'homogénéité, et d'une abstraction, le réseau d'interaction des catalyseurs, auxquels sont associés des indices d'intrication. Nous présentons ensuite la mise en place d'outils spécifiques pour l'analyse visuelle des réseaux complexes qui tirent profit de cette méthodologie. Ces outils présente une vue double de deux réseaux,qui inclue une un algorithme de dessin, une interaction associant brossage d'une sélection et de multiples liens pré-attentifs. Nous terminons ce document par la présentation détaillée d'applications dans de multiples domaines.When it comes to comprehension of complex phenomena, humans need to understand what interactions lie within them.These interactions are often captured with complex networks. However, the interaction pluralism is often shallowed by traditional network models. We propose a new way to look at these phenomena through the lens of multiplex networks, in which catalysts are drivers of the interaction through substrates. To study the entanglement of a multiplex network is to study how edges intertwine, in other words, how catalysts interact. Our entanglement analysis results in a full set of new objects which completes traditional network approaches: the entanglement homogeneity and intensity of the multiplex network, and the catalyst interaction network, with for each catalyst, an entanglement index. These objects are very suitable for embedment in a visual analytics framework, to enable comprehension of a complex structure. We thus propose of visual setting with coordinated multiple views. We take advantage of mental mapping and visual linking to present simultaneous information of a multiplex network at three different levels of abstraction. We complete brushing and linking with a leapfrog interaction that mimics the back-and-forth process involved in users' comprehension. The method is validated and enriched through multiple applications including assessing group cohesion in document collections, and identification of particular associations in social networks.BORDEAUX1-Bib.electronique (335229901) / SudocSudocFranceF

New Fundamental Technologies in Data Mining

The progress of data mining technology and large public popularity establish a need for a comprehensive text on the subject. The series of books entitled by "Data Mining" address the need by presenting in-depth description of novel mining algorithms and many useful applications. In addition to understanding each section deeply, the two books present useful hints and strategies to solving problems in the following chapters. The contributing authors have highlighted many future research directions that will foster multi-disciplinary collaborations and hence will lead to significant development in the field of data mining

The Dynamics of Multi-Modal Networks

The widespread study of networks in diverse domains, including social, technological, and scientific settings, has increased the interest in statistical and machine learning techniques for network analysis. Many of these networks are complex, involving more than one kind of entity, and multiple relationship types, both changing over time. While there have been many network analysis methods proposed for problems such as network evolution, community detection, information diffusion and opinion leader identification, the majority of these methods assume a single entity type, a single edge type and often no temporal dynamics. One of the main shortcomings of these traditional techniques is their inadequacy for capturing higher-order dependencies often present in real, complex networks. To address these shortcomings, I focus on analysis and inference in dynamic, multi-modal, multi-relational networks, containing multiple entity types (such as people, social groups, organizations, locations, etc.), and different relationship types (such as friendship, membership, affiliation, etc.). An example from social network theory is a network describing users, organizations and interest groups, where users have different types of ties among each other, such as friendship, family ties, etc., as well as affiliation and membership links with organizations and interest groups. By considering the complex structure of these networks rather than limiting the analysis to a single entity or relationship type, I show how we can build richer predictive models that provide better understanding of the network dynamics, and thus result in better quality predictions. In the first part of my dissertation, I address the problems of network evolution and clustering. For network evolution, I describe methods for modeling the interactions between different modalities, and propose a co-evolution model for social and affiliation networks. I then move to the problem of network clustering, where I propose a novel algorithm for clustering multi-modal, multi-relational data. The second part of my dissertation focuses on the temporal dynamics of interactions in complex networks, from both user-level and network-level perspectives. For the user-centric approach, I analyze the dynamics of user relationships with other entity types, proposing a measure of the "loyalty" a user shows for a given group or topic, based on her temporal interaction pattern. I then move to macroscopic-level approaches for analyzing the dynamic processes that occur on a network scale. I propose a new differential adaptive diffusion model for incorporating diversity and trust in the process of information diffusion on multi-modal, multi-relational networks. I also discuss the implications of the proposed diffusion model on designing new strategies for viral marketing and influential detection. I validate all the proposed methods on several real-world networks from multiple domains

Explorative Graph Visualization

Netzwerkstrukturen (Graphen) sind heutzutage weit verbreitet. Ihre Untersuchung dient dazu, ein besseres Verständnis ihrer Struktur und der durch sie modellierten realen Aspekte zu gewinnen. Die Exploration solcher Netzwerke wird zumeist mit Visualisierungstechniken unterstützt. Ziel dieser Arbeit ist es, einen Überblick über die Probleme dieser Visualisierungen zu geben und konkrete Lösungsansätze aufzuzeigen. Dabei werden neue Visualisierungstechniken eingeführt, um den Nutzen der geführten Diskussion für die explorative Graphvisualisierung am konkreten Beispiel zu belegen.Network structures (graphs) have become a natural part of everyday life and their analysis helps to gain an understanding of their inherent structure and the real-world aspects thereby expressed. The exploration of graphs is largely supported and driven by visual means. The aim of this thesis is to give a comprehensive view on the problems associated with these visual means and to detail concrete solution approaches for them. Concrete visualization techniques are introduced to underline the value of this comprehensive discussion for supporting explorative graph visualization

L'extraction d'information des sources de données non structurées et semi-structurées

L'objectif de la thèse: Dans le contexte des dépôts de connaissances de grandes dimensions récemment apparues, on exige l'investigation de nouvelles méthodes innovatrices pour résoudre certains problèmes dans le domaine de l'Extraction de l'Information (EI), tout comme dans d'autres sous-domaines apparentés. La thèse débute par un tour d'ensemble dans le domaine de l'Extraction de l'Information, tout en se concentrant sur le problème de l'identification des entités dans des textes en langage naturel. Cela constitue une démarche nécessaire pour tout système EI. L'apparition des dépôts de connaissances de grandes dimensions permet le traitement des sous-problèmes de désambigüisation au Niveau du Sens (WSD) et La Reconnaissance des Entités dénommées (NER) d'une manière unifiée. Le premier système implémenté dans cette thèse identifie les entités (les noms communs et les noms propres) dans un texte libre et les associe à des entités dans une ontologie, pratiquement, tout en les désambigüisant. Un deuxième système implémenté, inspiré par l'information sémantique contenue dans les ontologies, essaie, également, l'utilisation d'une nouvelle méthode pour la solution du problème classique de classement de texte, obtenant de bons résultats.Thesis objective: In the context of recently developed large scale knowledge sources (general ontologies), investigate possible new approaches to major areas of Information Extraction (IE) and related fields. The thesis overviews the field of Information Extraction and focuses on the task of entity recognition in natural language texts, a required step for any IE system. Given the availability of large knowledge resources in the form of semantic graphs, an approach that treats the sub-tasks of Word Sense Disambiguation and Named Entity Recognition in a unified manner is possible. The first implemented system using this approach recognizes entities (words, both common and proper nouns) from free text and assigns them ontological classes, effectively disambiguating them. A second implemented system, inspired by the semantic information contained in the ontologies, also attempts a new approach to the classic problem of text classification, showing good results