Developmment and Application of Ligand-based and Structure-based Computational Drug Discovery Tools Based on Frequent Subgraph Mining of Chemical Structures

Recent development in subgraph mining tools resulted in faster and more efficient algorithms that facilitate exploring the information encoded in data that can be represented by graphs. In this dissertation, we apply the graph mining technique to design ligand-based and structure-based computational drug discovery tools. For ligand-based drug design, molecules in a dataset will be represented by graphs, and subgraph mining tools will be used to find the frequent subgraphs (chemical fragments) that occur in at least a certain percentage of the ligands in the dataset. These chemical fragments will be used as molecular descriptors for the quantitative structure-activity relationship (QSAR) studies. They will also be used for identifying the pharmacophores responsible for the activity as well as the toxicophores responsible for the toxicity of a datasets of molecules. For the structure-based drug design, interacting atoms at the interface of a set of protein-ligand complexes will be represented by graphs. Frequent subgraphs identified will define the patterns of chemical interactions at the interface, which will be used to pose-score docked complexes to identify the correct docking pose

Concept graphs: Applications to biomedical text categorization and concept extraction

As science advances, the underlying literature grows rapidly providing valuable knowledge mines for researchers and practitioners. The text content that makes up these knowledge collections is often unstructured and, thus, extracting relevant or novel information could be nontrivial and costly. In addition, human knowledge and expertise are being transformed into structured digital information in the form of vocabulary databases and ontologies. These knowledge bases hold substantial hierarchical and semantic relationships of common domain concepts. Consequently, automating learning tasks could be reinforced with those knowledge bases through constructing human-like representations of knowledge. This allows developing algorithms that simulate the human reasoning tasks of content perception, concept identification, and classification. This study explores the representation of text documents using concept graphs that are constructed with the help of a domain ontology. In particular, the target data sets are collections of biomedical text documents, and the domain ontology is a collection of predefined biomedical concepts and relationships among them. The proposed representation preserves those relationships and allows using the structural features of graphs in text mining and learning algorithms. Those features emphasize the significance of the underlying relationship information that exists in the text content behind the interrelated topics and concepts of a text document. The experiments presented in this study include text categorization and concept extraction applied on biomedical data sets. The experimental results demonstrate how the relationships extracted from text and captured in graph structures can be used to improve the performance of the aforementioned applications. The discussed techniques can be used in creating and maintaining digital libraries through enhancing indexing, retrieval, and management of documents as well as in a broad range of domain-specific applications such as drug discovery, hypothesis generation, and the analysis of molecular structures in chemoinformatics

Coping with new Challenges in Clustering and Biomedical Imaging

The last years have seen a tremendous increase of data acquisition in different scientific fields such as molecular biology, bioinformatics or biomedicine. Therefore, novel methods are needed for automatic data processing and analysis of this large amount of data. Data mining is the process of applying methods like clustering or classification to large databases in order to uncover hidden patterns. Clustering is the task of partitioning points of a data set into distinct groups in order to minimize the intra cluster similarity and to maximize the inter cluster similarity. In contrast to unsupervised learning like clustering, the classification problem is known as supervised learning that aims at the prediction of group membership of data objects on the basis of rules learned from a training set where the group membership is known. Specialized methods have been proposed for hierarchical and partitioning clustering. However, these methods suffer from several drawbacks. In the first part of this work, new clustering methods are proposed that cope with problems from conventional clustering algorithms. ITCH (Information-Theoretic Cluster Hierarchies) is a hierarchical clustering method that is based on a hierarchical variant of the Minimum Description Length (MDL) principle which finds hierarchies of clusters without requiring input parameters. As ITCH may converge only to a local optimum we propose GACH (Genetic Algorithm for Finding Cluster Hierarchies) that combines the benefits from genetic algorithms with information-theory. In this way the search space is explored more effectively. Furthermore, we propose INTEGRATE a novel clustering method for data with mixed numerical and categorical attributes. Supported by the MDL principle our method integrates the information provided by heterogeneous numerical and categorical attributes and thus naturally balances the influence of both sources of information. A competitive evaluation illustrates that INTEGRATE is more effective than existing clustering methods for mixed type data. Besides clustering methods for single data objects we provide a solution for clustering different data sets that are represented by their skylines. The skyline operator is a well-established database primitive for finding database objects which minimize two or more attributes with an unknown weighting between these attributes. In this thesis, we define a similarity measure, called SkyDist, for comparing skylines of different data sets that can directly be integrated into different data mining tasks such as clustering or classification. The experiments show that SkyDist in combination with different clustering algorithms can give useful insights into many applications. In the second part, we focus on the analysis of high resolution magnetic resonance images (MRI) that are clinically relevant and may allow for an early detection and diagnosis of several diseases. In particular, we propose a framework for the classification of Alzheimer's disease in MR images combining the data mining steps of feature selection, clustering and classification. As a result, a set of highly selective features discriminating patients with Alzheimer and healthy people has been identified. However, the analysis of the high dimensional MR images is extremely time-consuming. Therefore we developed JGrid, a scalable distributed computing solution designed to allow for a large scale analysis of MRI and thus an optimized prediction of diagnosis. In another study we apply efficient algorithms for motif discovery to task-fMRI scans in order to identify patterns in the brain that are characteristic for patients with somatoform pain disorder. We find groups of brain compartments that occur frequently within the brain networks and discriminate well among healthy and diseased people

Proceedings. 19. Workshop Computational Intelligence, Dortmund, 2. - 4. Dezember 2009

Dieser Tagungsband enthält die Beiträge des 19. Workshops „Computational Intelligence“ des Fachausschusses 5.14 der VDI/VDE-Gesellschaft für Mess- und Automatisierungstechnik (GMA) und der Fachgruppe „Fuzzy-Systeme und Soft-Computing“ der Gesellschaft für Informatik (GI), der vom 2.-4. Dezember 2009 im Haus Bommerholz bei Dortmund stattfindet