Computational Tools for the Untargeted Assignment of FT-MS Metabolomics Datasets

Metabolomics is the study of metabolomes, the sets of metabolites observed in living systems. Metabolism interconverts these metabolites to provide the molecules and energy necessary for life processes. Many disease processes, including cancer, have a significant metabolic component that manifests as differences in what metabolites are present and in what quantities they are produced and utilized. Thus, using metabolomics, differences between metabolomes in disease and non-disease states can be detected and these differences improve our understanding of disease processes at the molecular level. Despite the potential benefits of metabolomics, the comprehensive investigation of metabolomes remains difficult. A popular analytical technique for metabolomics is mass spectrometry. Advances in Fourier transform mass spectrometry (FT-MS) instrumentation have yielded simultaneous improvements in mass resolution, mass accuracy, and detection sensitivity. In the metabolomics field, these advantages permit more complicated, but more informative experimental designs such as the use of multiple isotope-labeled precursors in stable isotope-resolved metabolomics (SIRM) experiments. However, despite these potential applications, several outstanding problems hamper the use of FT-MS for metabolomics studies. First, artifacts and data quality problems in FT-MS spectra can confound downstream data analyses, confuse machine learning models, and complicate the robust detection and assignment of metabolite features. Second, the assignment of observed spectral features to metabolites remains difficult. Existing targeted approaches for assignment often employ databases of known metabolites; however, metabolite databases are incomplete, thus limiting or biasing assignment results. Additionally, FT-MS provides limited structural information for observed metabolites, which complicates the determination of metabolite class (e.g. lipid, sugar, etc. ) for observed metabolite spectral features, a necessary step for many metabolomics experiments. To address these problems, a set of tools were developed. The first tool identifies artifacts with high peak density observed in many FT-MS spectra and removes them safely. Using this tool, two previously unreported types of high peak density artifact were identified in FT-MS spectra: fuzzy sites and partial ringing. Fuzzy sites were particularly problematic as they confused and reduced the accuracy of machine learning models trained on datasets containing these artifacts. Second, a tool called SMIRFE was developed to assign isotope-resolved molecular formulas to observed spectral features in an untargeted manner without a database of expected metabolites. This new untargeted method was validated on a gold-standard dataset containing both unlabeled and 15N-labeled compounds and was able to identify 18 of 18 expected spectral features. Third, a collection of machine learning models was constructed to predict if a molecular formula corresponds to one or more lipid categories. These models accurately predict the correct one of eight lipid categories on our training dataset of known lipid and non-lipid molecular formulas with precisions and accuracies over 90% for most categories. These models were used to predict lipid categories for untargeted SMIRFE-derived assignments in a non-small cell lung cancer dataset. Subsequent differential abundance analysis revealed a sub-population of non-small cell lung cancer samples with a significantly increased abundance in sterol lipids. This finding implies a possible therapeutic role of statins in the treatment and/or prevention of non-small cell lung cancer. Collectively these tools represent a pipeline for FT-MS metabolomics datasets that is compatible with isotope labeling experiments. With these tools, more robust and untargeted metabolic analyses of disease will be possible

Symbolic approaches and artificial intelligence algorithms for solving multi-objective optimisation problems

Problems that have more than one objective function are of great importance in engineering sciences and many other disciplines. This class of problems are known as multi-objective optimisation problems (or multicriteria). The difficulty here lies in the conflict between the various objective functions. Due to this conflict, one cannot find a single ideal solution which simultaneously satisfies all the objectives. But instead one can find the set of Pareto-optimal solutions (Pareto-optimal set) and consequently the Pareto-optimal front is established. Finding these solutions plays an important role in multi-objective optimisation problems and mathematically the problem is considered to be solved when the Pareto-optimal set, i.e. the set of all compromise solutions is found. The Pareto-optimal set may contain information that can help the designer make a decision and thus arrive at better trade-off solutions. The aim of this research is to develop new multi-objective optimisation symbolic algorithms capable of detecting relationship(s) among decision variables that can be used for constructing the analytical formula of Pareto-optimal front based on the extension of the current optimality conditions. A literature survey of theoretical and evolutionary computation techniques for handling multiple objectives, constraints and variable interaction highlights a lack of techniques to handle variable interaction. This research, therefore, focuses on the development of techniques for detecting the relationships between the decision variables (variable interaction) in the presence of multiple objectives and constraints. It attempts to fill the gap in this research by formally extending the theoretical results (optimality conditions). The research then proposes first-order multi-objective symbolic algorithm or MOSA-I and second-order multi-objective symbolic algorithm or MOSA-II that are capable of detecting the variable interaction. The performance of these algorithms is analysed and compared to a current state-of-the-art optimisation algorithm using popular test problems. The performance of the MOSA-II algorithm is finally validated using three appropriately chosen problems from literature. In this way, this research proposes a fully tested and validated methodology for dealing with multi-objective optimisation problems. In conclusion, this research proposes two new symbolic algorithms that are used for identifying the variable interaction responsible for constructing Pareto-optimal front among objectives in multi-objective optimisation problems. This is completed based on a development and relaxation of the first and second-order optimality conditions of Karush-Kuhn-Tucker.EThOS - Electronic Theses Online ServiceGBUnited Kingdo

The art of clustering bandits.

Multi-armed bandit problems are receiving a great deal of attention because they adequately formalize the exploration-exploitation trade-offs arising in several industrially relevant applications, such as online advertisement and, more generally, recommendation systems. In many cases, however, these applications have a strong social component, whose integration in the bandit algorithms could lead to a dramatic performance increase. For instance, we may want to serve content to a group of users by taking advantage of an underlying network of social relationships among them. The purpose of this thesis is to introduce novel and principled algorithmic approaches to the solution of such networked bandit problems. Starting from a global (Laplacian-based) strategy which allocates a bandit algorithm to each network node (user), and allows it to "share" signals (contexts and payoffs) with the neghboring nodes, our goal is to derive and experimentally test more scalable approaches based on different ways of clustering the graph nodes. More importantly, we shall investigate the case when the graph structure is not given ahead of time, and has to be inferred based on past user behavior. A general difficulty arising in such practical scenarios is that data sequences are typically nonstationary, implying that traditional statistical inference methods should be used cautiously, possibly replacing them with by more robust nonstochastic (e.g., game-theoretic) inference methods. In this thesis, we will firstly introduce the centralized clustering bandits. Then, we propose the corresponding solution in decentralized scenario. After that, we explain the generic collaborative clustering bandits. Finally, we extend and showcase the state-of-the-art clustering bandits that we developed in the quantification problem

Sensor Signal and Information Processing II

In the current age of information explosion, newly invented technological sensors and software are now tightly integrated with our everyday lives. Many sensor processing algorithms have incorporated some forms of computational intelligence as part of their core framework in problem solving. These algorithms have the capacity to generalize and discover knowledge for themselves and learn new information whenever unseen data are captured. The primary aim of sensor processing is to develop techniques to interpret, understand, and act on information contained in the data. The interest of this book is in developing intelligent signal processing in order to pave the way for smart sensors. This involves mathematical advancement of nonlinear signal processing theory and its applications that extend far beyond traditional techniques. It bridges the boundary between theory and application, developing novel theoretically inspired methodologies targeting both longstanding and emergent signal processing applications. The topic ranges from phishing detection to integration of terrestrial laser scanning, and from fault diagnosis to bio-inspiring filtering. The book will appeal to established practitioners, along with researchers and students in the emerging field of smart sensors processing

Advances in Human-Robot Interaction

Rapid advances in the field of robotics have made it possible to use robots not just in industrial automation but also in entertainment, rehabilitation, and home service. Since robots will likely affect many aspects of human existence, fundamental questions of human-robot interaction must be formulated and, if at all possible, resolved. Some of these questions are addressed in this collection of papers by leading HRI researchers

Geometry of Quantum States from Symmetric Informationally Complete Probabilities

It is usually taken for granted that the natural mathematical framework for quantum mechanics is the theory of Hilbert spaces, where pure states of a quantum system correspond to complex vectors of unit length. These vectors can be combined to create more general states expressed in terms of positive semidefinite matrices of unit trace called density operators. A density operator tells us everything we know about a quantum system. In particular, it specifies a unique probability for any measurement outcome. Thus, to fully appreciate quantum mechanics as a statistical model for physical phenomena, it is necessary to understand the basic properties of its set of states. Studying the convex geometry of quantum states provides important clues as to why the theory is expressed most naturally in terms of complex amplitudes. At the very least, it gives us a new perspective into thinking about structure of quantum mechanics. This thesis is concerned with the structure of quantum state space obtained from the geometry of the convex set of probability distributions for a special class of measurements called symmetric informationally complete (SIC) measurements. In this context, quantum mechanics is seen as a particular restriction of a regular simplex, where the state space is postulated to carry a symmetric set of states called SICs, which are associated with equiangular lines in a complex vector space. The analysis applies specifically to 3-dimensional quantum systems or qutrits, which is the simplest nontrivial case to consider according to Gleason's theorem. It includes a full characterization of qutrit SICs and includes specific proposals for implementing them using linear optics. The infinitely many qutrit SICs are classified into inequivalent families according to the Clifford group, where equivalence is defined by geometrically invariant numbers called triple products. The multiplication of SIC projectors is also used to define structure coefficients, which are convenient for elucidating some additional structure possessed by SICs, such as the Lie algebra associated with the operator basis defined by SICs, and a linear dependency structure inherited from the Weyl-Heisenberg symmetry. After describing the general one-to-one correspondence between density operators and SIC probabilities, many interesting features of the set of qutrits are described, including an elegant formula for its pure states, which reveals a permutation symmetry related to the structure of a finite affine plane, the exact rotational equivalence of different SIC probability spaces, the shape of qutrit state space defined by the radial distance of the boundary from the maximally mixed state, and a comparison of the 2-dimensional cross-sections of SIC probabilities to known results. Towards the end, the representation of quantum states in terms of SICs is used to develop a method for reconstructing quantum theory from the postulate of maximal consistency, and a procedure for building up qutrit state space from a finite set of points corresponding to a Hesse configuration in Hilbert space is sketched briefly

Six Decades of Flight Research: An Annotated Bibliography of Technical Publications of NASA Dryden Flight Research Center, 1946-2006

Titles, authors, report numbers, and abstracts are given for nearly 2900 unclassified and unrestricted technical reports and papers published from September 1946 to December 2006 by the NASA Dryden Flight Research Center and its predecessor organizations. These technical reports and papers describe and give the results of 60 years of flight research performed by the NACA and NASA, from the X-1 and other early X-airplanes, to the X-15, Space Shuttle, X-29 Forward Swept Wing, X-31, and X-43 aircraft. Some of the other research airplanes tested were the D-558, phase 1 and 2; M-2, HL-10 and X-24 lifting bodies; Digital Fly-By-Wire and Supercritical Wing F-8; XB-70; YF-12; AFTI F-111 TACT and MAW; F-15 HiDEC; F-18 High Alpha Research Vehicle, F-18 Systems Research Aircraft and the NASA Landing Systems Research aircraft. The citations of reports and papers are listed in chronological order, with author and aircraft indices. In addition, in the appendices, citations of 270 contractor reports, more than 200 UCLA Flight System Research Center reports, nearly 200 Tech Briefs, 30 Dryden Historical Publications, and over 30 videotapes are included