Construction of phylogenetic trees by kernel-based comparative analysis of metabolic networks

BACKGROUND: To infer the tree of life requires knowledge of the common characteristics of each species descended from a common ancestor as the measuring criteria and a method to calculate the distance between the resulting values of each measure. Conventional phylogenetic analysis based on genomic sequences provides information about the genetic relationships between different organisms. In contrast, comparative analysis of metabolic pathways in different organisms can yield insights into their functional relationships under different physiological conditions. However, evaluating the similarities or differences between metabolic networks is a computationally challenging problem, and systematic methods of doing this are desirable. Here we introduce a graph-kernel method for computing the similarity between metabolic networks in polynomial time, and use it to profile metabolic pathways and to construct phylogenetic trees. RESULTS: To compare the structures of metabolic networks in organisms, we adopted the exponential graph kernel, which is a kernel-based approach with a labeled graph that includes a label matrix and an adjacency matrix. To construct the phylogenetic trees, we used an unweighted pair-group method with arithmetic mean, i.e., a hierarchical clustering algorithm. We applied the kernel-based network profiling method in a comparative analysis of nine carbohydrate metabolic networks from 81 biological species encompassing Archaea, Eukaryota, and Eubacteria. The resulting phylogenetic hierarchies generally support the tripartite scheme of three domains rather than the two domains of prokaryotes and eukaryotes. CONCLUSION: By combining the kernel machines with metabolic information, the method infers the context of biosphere development that covers physiological events required for adaptation by genetic reconstruction. The results show that one may obtain a global view of the tree of life by comparing the metabolic pathway structures using meta-level information rather than sequence information. This method may yield further information about biological evolution, such as the history of horizontal transfer of each gene, by studying the detailed structure of the phylogenetic tree constructed by the kernel-based method

An approximate search engine for structure

As the size of structural databases grows, the need for efficiently searching these databases arises. Thanks to previous and ongoing research, searching by attribute-value and by text has become commonplace in these databases. However, searching by topological or physical structure, especially for large databases and especially for approximate matches, is still an art. In this dissertation, efficient search techniques are presented for retrieving trees from a database that are similar to a given query tree. Rooted ordered labeled trees, rooted unordered labeled trees and free trees are considered. Ordered labeled trees are trees in which each node has a label and the left-to-right order among siblings matters. Unordered labeled trees are trees in which the parent-child relationship is significant, but the order among siblings is unimportant. Free trees (unrooted unordered trees) are acyclic graphs. These trees find many applications in bioinformatics, Web log analysis, phyloinformatics, XML processing, etc. Two types of similarity measures are investigated: (i) counting the mismatching paths in the query tree and a data tree, and (ii) measuring the topological relationship between the trees. The proposed approaches include storing the paths of trees in a suffix array, employing hashing techniques to speed up retrieval, and counting the number of up-down operations to move a token from one node to another node in a tree. Various filters for accelerating a search, different strategies for parallelizing these search algorithms and applications of these algorithms to XML and phylogenetic data management are discussed. The proposed techniques have been implemented into a phylogenetic search engine which is fully operational and is available on the World Wide Web. Experimental results on comparing the similarity measures with existing tree metrics and on evaluating the efficiency of the search techniques demonstrate the effectiveness of the search engine. Future work includes extending the techniques to other structural data, as well as developing new filters and algorithms for speeding up searching and mining in complex structures

Information retrieval and mining in high dimensional databases

This dissertation is composed of two parts. In the first part, we present a framework for finding information (more precisely, active patterns) in three dimensional (3D) graphs. Each node in a graph is an undecoraposable or atomic unit and has a label. Edges are links between the atomic units. Patterns are rigid substructures that may occur in a graph after allowing for an arbitrary number of whole-structure rotations and translations as well as a small number (specified by the user) of edit operations in the patterns or in the graph. (When a pattern appears in a graph only after the graph has been modified, we call that appearance approximate occurrence. ) The edit operations include relabeling a node, deleting a node and inserting a node. The proposed method is based on the geometric hashing technique, which hashes node-triplets of the graphs into a 3D table and compresses the label-triplets in the table. To demonstrate the utility of our algorithms, we discuss two applications of them in scientific data mining. First, we apply the method to locating frequently occurring motifs in two families of proteins pertaining to RNA-directed DNA Polymerase and Thymidylate Synthase, and use the motifs to classify the proteins. Then we apply the method to clustering chemical compounds pertaining to aromatic, bicyclicalkanes and photosynthesis. Experimental results indicate the good performance of our algorithms and high recall and precision rates for both classification and clustering. We also extend our algorithms for processing a class of similarity queries in databases of 3D graphs. In the second part of the dissertation, we present an index structure, called MetricMap, that takes a set of objects and a distance metric and then maps those objects to a k-dimensional pseudo-Euclidean space in such a way that the distances among objects are approximately preserved. Our approach employs sampling and the calculation of eigenvalues and eigenvectors. The index structure is a useful tool for clustering and visualization in data intensive applications, because it replaces expensive distance calculations by sum-of-square calculations. This can make clustering in large databases with expensive distance metrics practical. We compare the index structure with another data mining index structure, FastMap, proposed by Faloutsos and Lin, according to two criteria: relative error and clustering accuracy. For relative error, we show that (i) FastMap gives a lower relative error than MetrieMap for Euclidean distances, (ii) MetricMap gives a lower relative error than Fast Map for non-Euclidean distances (i.e., general distance metrics), and (iii) combining the two reduces the error yet further. A similar result is obtained when comparing the accuracy of clustering. These results hold for different data sizes. The main qualitative conclusion is that these two index structures capture complenleiltary information about distance metrics and therefore can be used together to great benefit. The net effect is that multi-day computations can be done in minutes. We have implemented the proposed algorithms and the MetricMap index structure into a toolkit. This toolkit will be useful for data mining, visualization, and approximate retrieval in scientific, multimedia and high dimensional databases

DE LA MODELISATION A L'EXPLOITATION DES DOCUMENTS A STRUCTURES MULTIPLES

With the recent development of new information and communication technologies, the paper documents are transformed to digital documents. Furthermore, it considers that the document is no longer seen as a whole, or as a monolithic bloc, but as organized entities. Exploiting these documents amount to identify and locate these entities. These entities are connected by relationships to give a "form" to document. Several types of relationships may occur, so that several "forms" of a document emerge. These different materializations of the same document are related to different uses of the same document and are essential for optimal management and shared of holdings. The work presented in this thesis aims to address the challenges of representing different materializations of a document through its representation of entities and their relationships. If those materializations are translated through structures, the issues are related to the representation of multistructured documents. Our work focuses mainly on the modeling, integration and exploitation of multistructured documents: (1) Proposal of multistructured document model. This model incorporates two levels of description: a specific level to describe each document through entities that compose and a generic level to identify document kinds through the grouping of similar structures. (2) Proposal of techniques for extracting structure (implicit or explicit) of a document (the specific level) and classification of this structure with respect to common structures (the generic level). The classification algorithm proposed includes a calculation of distance called "structural" (comparison of trees and graphs). This classification is associated with a process of verification of the "cohesion" of classes and possible reorganization of disrupted classes. (3) Proposal of document exploitation technical from their structures and their contents: (a) a document search that can reproduce documentary granules through criteria based on research of structures and / or content, (b) a multidimensional analysis that is to analyze and visualize the documentary information across multiple dimensions (of structures and / or content). In order to validate our proposals, we have developed a tool for integration and analysis of multistructured documents, called MDOCREP (Multistructured Document Repository). This tool provides on the one hand, the extraction and classification of document structures, and on the other hand, the querying and the multidimensional analysis of documents from their different structures.Avec l'évolution des nouvelles technologies de l'information et de la communication, les documents papier ont laissé la place aux documents numériques. On considère de plus que le document n'est plus vu comme un tout, ni comme un bloc monolithique, mais comme un ensemble organisé d'entités. Exploiter ces documents revient à identifier et retrouver ces entités. Ces dernières sont reliées par des relations permettant de donner une « forme » au document. Plusieurs types de relations peuvent apparaître, de sorte à ce que plusieurs « formes » d'un même document émergent. Ces différentes matérialisations d'un même document sont liées à des usages différents d'un même document et sont primordiales pour une gestion optimale et partagée des fonds documentaires. Les travaux présentés dans cette thèse visent à faire face aux défis de représentation des différentes matérialisations d'un document au travers de la représentation de ses entités et de leurs relations. Si ces matérialisations sont traduites par des structures, les enjeux concernent la représentation des documents à structures multiples. Nos travaux portent essentiellement sur la modélisation, l'intégration et l'exploitation des documents à structures multiples : (1) Proposition d'un modèle de documents multistructurés. Ce modèle intègre deux niveaux de description : un niveau spécifique permettant de décrire chaque document au travers des entités qui le composent et un niveau générique permettant de définir des typologies de documents au travers du regroupement de structures similaires. (2) Proposition des techniques d'extraction de structure (implicite ou explicite) d'un document (niveau spécifique) et de classification de cette structure par rapport à des structures communes (niveau générique). L'algorithme de classification proposé intègre un calcul d'une distance dite « structurelle » (comparaison d'arbres et de graphes). Cette démarche de classification est associée à une démarche de vérification de la « cohésion » des classes et de réorganisation éventuelle des classes perturbées. (3) Proposition de techniques d'exploitation des documents à partir de leurs structures et de leur contenu : (a) une recherche de documents qui permet de restituer des granules documentaires selon des critères de recherches basés sur la ou les structures et/ou le contenu ; (b) une analyse multidimensionnelle qui consiste à analyser et visualiser les informations documentaires selon plusieurs dimensions (de structures et/ou de contenu). Pour valider nos propositions, nous avons développé un outil d'aide à l'intégration et à l'analyse de documents à structures multiples, intitulé MDOCREP (Multistructured DOCument REPository). Cet outil assure d'une part, l'extraction et la classification des structures de documents, et d'autre part, l'interrogation et la restitution multidimensionnelle des documents à partir de leurs différentes structures