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Modern high-throughput technologies such as microarrays, next generation sequencing and mass spectrometry provide huge amounts of data per measurement and challenge traditional analyses. New strategies of data processing, visualization and functional analysis are inevitable. This thesis presents an approach which applies a machine learning technique known as self organizing maps (SOMs). SOMs enable the parallel sample- and feature-centered view of molecular phenotypes combined with strong visualization and second-level analysis capabilities. We developed a comprehensive analysis and visualization pipeline based on SOMs. The unsupervised SOM mapping projects the initially high number of features, such as gene expression profiles, to meta-feature clusters of similar and hence potentially co-regulated single features. This reduction of dimension is attained by the re-weighting of primary information and does not entail a loss of primary information in contrast to simple filtering approaches. The meta-data provided by the SOM algorithm is visualized in terms of intuitive mosaic portraits. Sample-specific and common properties shared between samples emerge as a handful of localized spots in the portraits collecting groups of co-regulated and co-expressed meta-features. This characteristic color patterns reflect the data landscape of each sample and promote immediate identification of (meta-)features of interest. It will be demonstrated that SOM portraits transform large and heterogeneous sets of molecular biological data into an atlas of sample-specific texture maps which can be directly compared in terms of similarities and dissimilarities. Spot-clusters of correlated meta-features can be extracted from the SOM portraits in a subsequent step of aggregation. This spot-clustering effectively enables reduction of the dimensionality of the data in two subsequent steps towards a handful of signature modules in an unsupervised fashion. Furthermore we demonstrate that analysis techniques provide enhanced resolution if applied to the meta-features. The improved discrimination power of meta-features in downstream analyses such as hierarchical clustering, independent component analysis or pairwise correlation analysis is ascribed to essentially two facts: Firstly, the set of meta-features better represents the diversity of patterns and modes inherent in the data and secondly, it also possesses the better signal-to-noise characteristics as a comparable collection of single features. Additionally to the pattern-driven feature selection in the SOM portraits, we apply statistical measures to detect significantly differential features between sample classes. Implementation of scoring measurements supplements the basal SOM algorithm. Further, two variants of functional enrichment analyses are introduced which link sample specific patterns of the meta-feature landscape with biological knowledge and support functional interpretation of the data based on the ‘guilt by association’ principle. Finally, case studies selected from different ‘OMIC’ realms are presented in this thesis. In particular, molecular phenotype data derived from expression microarrays (mRNA, miRNA), sequencing (DNA methylation, histone modification patterns) or mass spectrometry (proteome), and also genotype data (SNP-microarrays) is analyzed. It is shown that the SOM analysis pipeline implies strong application capabilities and covers a broad range of potential purposes ranging from time series and treatment-vs.-control experiments to discrimination of samples according to genotypic, phenotypic or taxonomic classifications.

Thesis (Ph. D.)--University of Florida, 2001. / Title from first page of PDF file. Document formatted into pages; contains ix, 117 p.; also contains graphics. Vita. Includes bibliographical references (p. 109-116).

The aim of the project was to identify biologically relevant novel gene clusters by using combined genomic data instead of using only gene expression data in isolation. The clustering algorithm based on self-organizing maps (Kasturi et al., 2005) was extended and implemented in order to use gene location data together with the gene expression and the motif occurrence data for gene clustering. A distance function was defined to be used with gene location data. The algorithm was also extended in order to use vector angle distance for gene expression data. Arabidopsis thaliana is chosen as a data source to evaluate the developed algorithm. A test data set was created by using 100 Arabidopsis genes that have gene expression data with seven different time points during cold stress condition, motif occurrence data which indicates the occurrence frequency of 614 different motifs and the chromosomal location data of each gene. Gene Ontology (http://www.geneontology.org) and TAIR (http://arabidopsis.org) databases were used to find the molecular function and biological process information of each gene in order to examine the biological accuracy of newly discovered clusters after using combined genomic data. The biological evaluation of the results showed that using combined genomic data to cluster genes resulted in new biologically relevant clusters.

With the growth of computer networks and the advancement of hardware technologies, unprecedented access to data volumes become accessible in a distributed fashion forming heterogeneous data sources. Understanding and combining these data into data warehouses, or merging remote public data into existing databases can significantly enrich the information provided by these data. This problem is called data integration: combining data residing at different sources, and providing the user with a unified view of these data. There are two issues with making use of remote data sources: (1) discovery of relevant data sources, and (2) performing the proper joins between the local data source and the relevant remote databases. Both can be solved if one can effectively identify semantically-related attributes between the local data sources and the available remote data sources. However, performing these tasks manually is time-consuming because of the large data sizes and the unavailability of schema documentation; therefore, an automated tool would be definitely more suitable. Automatically detecting similar entities based on the content is challenging due to three factors. First, because the amount of records is voluminous, it is difficult to perceive or discover information structures or relationships. Second, the schemas of the databases are unfamiliar; therefore, detecting relevant data is difficult. Third, the database entity types are heterogeneous and there is no existing solution for extracting a richer classification result from the processing of two different data types, or at least from textual and numerical data. We propose to utilize self-organizing maps (SOM) to aid the visual exploration of the large data volumes. The unsupervised classification property of SOM facilitates the integration of completely unfamiliar relational database tables and attributes based on the contents. In order to accommodate heterogeneous data types found in relational databases, we extended the term frequency – inverse document frequency (TF-IDF) measure to handle numerical and textual attribute types by unified vectorization processing. The resulting map allows the user to browse the heterogeneously typed database attributes and discover clusters of documents (attributes) having similar content. iii The discovered clusters can significantly aid in manual or automated constructions of data integrity constraints in data cleaning or schema mappings for data integration.

This dissertation develops a "neighborhood" based neural network model utilizing wavelet analysis and Self-organizing Map (SOM) to predict building baseline energy use. Wavelet analysis was used for feature extraction of the daily weather profiles. The resulting few significant wavelet coefficients represent not only average but also variation of the weather components. A SOM is used for clustering and projecting high-dimensional data into usually a one or two dimensional map to reveal the data structure which is not clear by visual inspection. In this study, neighborhoods that contain days with similar meteorological conditions are classified by a SOM using significant wavelet coefficients; a baseline model is then developed for each neighborhood. In each neighborhood, modeling is more robust without unnecessary compromises that occur in global predictor regression models. This method was applied to the Energy Predictor Shootout II dataset and compared with the winning entries for hourly energy use predictions. A comparison between the "neighborhood" based linear regression model and the change-point model for daily energy use prediction was also performed. We also studied the application of the non-parametric nearest neighborhood points approach in determining the uncertainty of energy use prediction. The uncertainty from "local" system behavior rather than from global statistical indices such as root mean square error and other measures is shown to be more realistic and credible than the statistical approaches currently used. In general, a baseline model developed by local system behavior is more reliable than a global baseline model. The "neighborhood" based neural network model was found to predict building baseline energy use more accurately and achieve more reliable estimation of energy savings as well as the associated uncertainties in energy savings from building retrofits.

This project utilized synthesis and in vitro assays to generate antagonist SARs at various nAChR subtypes. Alkylation of the pyridino nitrogen of the nicotine molecule afforded subtype specific antagonists at a42* nAChR subtypes and nAChR subtypes that mediate nicotine-evoked dopamine release. Using this data, a series of mono-azaaromatic quaternary salts were produced and evaluated in binding and functional assays for a42* and a7* nAChR subtypes and nAChR subtypes that mediate nicotine-evoked dopamine release. Additionally, bis-azaaromatic quaternary salts were synthesized and evaluated in the same assays. Two potent lead compounds were identified. N-n-dodecylnicotinium iodide (NDDNI) was found to be very potent at both a42* nAChR subtypes and nAChR subtypes that mediate nicotine-evoked dopamine release. And the most promising candidate was N-N-bisdodecylpicolinium dibromide (bDDPiB), which was selective for the nAChR subtypes that mediate nicotine-evoked dopamine release (IC50 = 9 nM). Additionally, using the data from the SARs, predictive computer models were generated to assist in future compound assessment without in vitro assays. Three self-organizing map (SOMs) models were generated from three different sets of compounds. The groups consisted of the mono-substituted compounds, the bissubstituted compounds, and both sets combined. The models were able to successfully "bin" the test set of compounds after developing a model from a similar set of training compounds. Additionally, using genetic functional activity (GFA) algorithms an evolutionary approach to generating predictive model equations was applied to the compounds. Three separate equations were generated in order to form a predictive method for evaluating affinities at the a4b2* receptor subtype. In addition to the modeling and SAR work of the quaternary ammonium compounds, novel synthetic methods were also employed to develop enantiomerically pure nicotine analogs. Efficient enantioselective syntheses of (S)- and R-(+)-nornicotine, (S)-and R-(+)-anabasine, and (S)-and R-(+)-anatabine have been developed, affording isomers in high enantiomeric excess.

Thesis (Ph.D.) - Carleton University, 2005. / Includes bibliographical references (p. 127-139). Also available in electronic format on the Internet.

Thesis (Ph. D.)--University of Florida, 2004. / Title from title page of source document. Document formatted into pages; contains 130 pages. Includes vita. Includes bibliographical references.

Thesis (Ph.D.) - University of Queensland, 2006. / Includes bibliography.