High Dimensional Data Set Analysis Using a Large-Scale Manifold Learning Approach

Because of technological advances, a trend occurs for data sets increasing in size and dimensionality. Processing these large scale data sets is challenging for conventional computers due to computational limitations. A framework for nonlinear dimensionality reduction on large databases is presented that alleviates the issue of large data sets through sampling, graph construction, manifold learning, and embedding. Neighborhood selection is a key step in this framework and a potential area of improvement. The standard approach to neighborhood selection is setting a fixed neighborhood. This could be a fixed number of neighbors or a fixed neighborhood size. Each of these has its limitations due to variations in data density. A novel adaptive neighbor-selection algorithm is presented to enhance performance by incorporating sparse ℓ 1-norm based optimization. These enhancements are applied to the graph construction and embedding modules of the original framework. As validation of the proposed ℓ1-based enhancement, experiments are conducted on these modules using publicly available benchmark data sets. The two approaches are then applied to a large scale magnetic resonance imaging (MRI) data set for brain tumor progression prediction. Results showed that the proposed approach outperformed linear methods and other traditional manifold learning algorithms

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

Characterization and Reduction of Noise in Manifold Representations of Hyperspectral Imagery

A new workflow to produce dimensionality reduced manifold coordinates based on the improvements of landmark Isometric Mapping (ISOMAP) algorithms using local spectral models is proposed. Manifold space from nonlinear dimensionality reduction better addresses the nonlinearity of the hyperspectral data and often has better per- formance comparing to the results of linear methods such as Minimum Noise Fraction (MNF). The dissertation mainly focuses on using adaptive local spectral models to fur- ther improve the performance of ISOMAP algorithms by addressing local noise issues and perform guided landmark selection and nearest neighborhood construction in local spectral subsets. This work could benefit the performance of common hyperspectral image analysis tasks, such as classification, target detection, etc., but also keep the computational burden low. This work is based on and improves the previous ENH- ISOMAP algorithm in various ways. The workflow is based on a unified local spectral subsetting framework. Embedding spaces in local spectral subsets as local noise models are first proposed and used to perform noise estimation, MNF regression and guided landmark selection in a local sense. Passive and active methods are proposed and ver- ified to select landmarks deliberately to ensure local geometric structure coverage and local noise avoidance. Then, a novel local spectral adaptive method is used to construct the k-nearest neighbor graph. Finally, a global MNF transformation in the manifold space is also introduced to further compress the signal dimensions. The workflow is implemented using C++ with multiple implementation optimizations, including using heterogeneous computing platforms that are available in personal computers. The re- sults are presented and evaluated by Jeffries-Matsushita separability metric, as well as the classification accuracy of supervised classifiers. The proposed workflow shows sig- nificant and stable improvements over the dimensionality reduction performance from traditional MNF and ENH-ISOMAP on various hyperspectral datasets. The computa- tional speed of the proposed implementation is also improved

Convex and non-convex optimization using centroid-encoding for visualization, classification, and feature selection

Includes bibliographical references.2022 Fall.Classification, visualization, and feature selection are the three essential tasks of machine learning. This Ph.D. dissertation presents convex and non-convex models suitable for these three tasks. We propose Centroid-Encoder (CE), an autoencoder-based supervised tool for visualizing complex and potentially large, e.g., SUSY with 5 million samples and high-dimensional datasets, e.g., GSE73072 clinical challenge data. Unlike an autoencoder, which maps a point to itself, a centroid-encoder has a modified target, i.e., the class centroid in the ambient space. We present a detailed comparative analysis of the method using various data sets and state-of-the-art techniques. We have proposed a variation of the centroid-encoder, Bottleneck Centroid-Encoder (BCE), where additional constraints are imposed at the bottleneck layer to improve generalization performance in the reduced space. We further developed a sparse optimization problem for the non-linear mapping of the centroid-encoder called Sparse Centroid-Encoder (SCE) to determine the set of discriminate features between two or more classes. The sparse model selects variables using the 1-norm applied to the input feature space. SCE extracts discriminative features from multi-modal data sets, i.e., data whose classes appear to have multiple clusters, by using several centers per class. This approach seems to have advantages over models which use a one-hot-encoding vector. We also provide a feature selection framework that first ranks each feature by its occurrence, and the optimal number of features is chosen using a validation set. CE and SCE are models based on neural network architectures and require the solution of non-convex optimization problems. Motivated by the CE algorithm, we have developed a convex optimization for the supervised dimensionality reduction technique called Centroid Component Retrieval (CCR). The CCR model optimizes a multi-objective cost by balancing two complementary terms. The first term pulls the samples of a class towards its centroid by minimizing a sample's distance from its class centroid in low dimensional space. The second term pushes the classes by maximizing the scattering volume of the ellipsoid formed by the class-centroids in embedded space. Although the design principle of CCR is similar to LDA, our experimental results show that CCR exhibits performance advantages over LDA, especially on high-dimensional data sets, e.g., Yale Faces, ORL, and COIL20. Finally, we present a linear formulation of Centroid-Encoder with orthogonality constraints, called Principal Centroid Component Analysis (PCCA). This formulation is similar to PCA, except the class labels are used to formulate the objective, resulting in the form of supervised PCA. We show the classification and visualization experiments results with this new linear tool

Enhancing Automatic Annotation for Optimal Image Retrieval

Image search and retrieval based on content is very cumbersome task particularly when the image database is large. The accuracy of the retrieval as well as the processing speed are two important measures used for assessing and comparing the effectiveness of various systems. Text retrieval is more mature and advanced than image content retrieval. In this dissertation, the focus is on converting image content into text tags that can be easily searched using standard search engines where the size and speed issues of the database have been already dealt with. Therefore, image tagging becomes an essential tool for image retrieval from large image databases. Automation of image tagging has received considerable attention by many researchers in recent years. The optimal goal of image description is to automatically annotate images with tags that semantically represent the image content. The speed and accuracy of Image retrieval from large databases are few of the important domains that can benefit from automatic tagging. In this work, several state of the art image classification and image tagging techniques are reviewed. We propose a new self-learning multilayered tagging framework that can address the limitations of current approaches and provide mutual accuracy improvement between the recognition layer and the annotation layer. Our results indicate that the proposed framework can improve the overall accuracy of information retrieval in a variety of image databases