Seleção genômica para características longitudinais de bovinos da raça Holandesa

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Approccio network-based alla discriminant analysis mediante HPC per la ricerca di signature ottimali in dati ad alta dimensionalità

Il presente lavoro di tesi si inserisce nell’ambito della classificazione di dati ad alta dimensionalità, sviluppando un algoritmo basato sul metodo della Discriminant Analysis. Esso classifica i campioni attraverso le variabili prese a coppie formando un network a partire da quelle che hanno una performance sufficientemente elevata. Successivamente, l’algoritmo si avvale di proprietà topologiche dei network (in particolare la ricerca di subnetwork e misure di centralità di singoli nodi) per ottenere varie signature (sottoinsiemi delle variabili iniziali) con performance ottimali di classificazione e caratterizzate da una bassa dimensionalità (dell’ordine di 101, inferiore di almeno un fattore 103 rispetto alle variabili di partenza nei problemi trattati). Per fare ciò, l’algoritmo comprende una parte di definizione del network e un’altra di selezione e riduzione della signature, calcolando ad ogni passaggio la nuova capacità di classificazione operando test di cross-validazione (k-fold o leave- one-out). Considerato l’alto numero di variabili coinvolte nei problemi trattati – dell’ordine di 104 – l’algoritmo è stato necessariamente implementato su High-Performance Computer, con lo sviluppo in parallelo delle parti più onerose del codice C++, nella fattispecie il calcolo vero e proprio del di- scriminante e il sorting finale dei risultati. L’applicazione qui studiata è a dati high-throughput in ambito genetico, riguardanti l’espressione genica a livello cellulare, settore in cui i database frequentemente sono costituiti da un numero elevato di variabili (104 −105) a fronte di un basso numero di campioni (101 −102). In campo medico-clinico, la determinazione di signature a bassa dimensionalità per la discriminazione e classificazione di campioni (e.g. sano/malato, responder/not-responder, ecc.) è un problema di fondamentale importanza, ad esempio per la messa a punto di strategie terapeutiche personalizzate per specifici sottogruppi di pazienti attraverso la realizzazione di kit diagnostici per l’analisi di profili di espressione applicabili su larga scala. L’analisi effettuata in questa tesi su vari tipi di dati reali mostra che il metodo proposto, anche in confronto ad altri metodi esistenti basati o me- no sull’approccio a network, fornisce performance ottime, tenendo conto del fatto che il metodo produce signature con elevate performance di classifica- zione e contemporaneamente mantenendo molto ridotto il numero di variabili utilizzate per questo scopo.

Visualization and validation of (Q)SAR models

Analyzing and modeling relationships between the structure of chemical compounds, their physico-chemical properties, and biological or toxic effects in chemical datasets is a challenging task for scientific researchers in the field of cheminformatics. Therefore, (Q)SAR model validation is essential to ensure future model predictivity on unseen compounds. Proper validation is also one of the requirements of regulatory authorities in order to approve its use in real-world scenarios as an alternative testing method. However, at the same time, the question of how to validate a (Q)SAR model is still under discussion. In this work, we empirically compare a k-fold cross-validation with external test set validation. The introduced workflow allows to apply the built and validated models to large amounts of unseen data, and to compare the performance of the different validation approaches. Our experimental results indicate that cross-validation produces (Q)SAR models with higher predictivity than external test set validation and reduces the variance of the results. Statistical validation is important to evaluate the performance of (Q)SAR models, but does not support the user in better understanding the properties of the model or the underlying correlations. We present the 3D molecular viewer CheS-Mapper (Chemical Space Mapper) that arranges compounds in 3D space, such that their spatial proximity reflects their similarity. The user can indirectly determine similarity, by selecting which features to employ in the process. The tool can use and calculate different kinds of features, like structural fragments as well as quantitative chemical descriptors. Comprehensive functionalities including clustering, alignment of compounds according to their 3D structure, and feature highlighting aid the chemist to better understand patterns and regularities and relate the observations to established scientific knowledge. Even though visualization tools for analyzing (Q)SAR information in small molecule datasets exist, integrated visualization methods that allows for the investigation of model validation results are still lacking. We propose visual validation, as an approach for the graphical inspection of (Q)SAR model validation results. New functionalities in CheS-Mapper 2.0 facilitate the analysis of (Q)SAR information and allow the visual validation of (Q)SAR models. The tool enables the comparison of model predictions to the actual activity in feature space. Our approach reveals if the endpoint is modeled too specific or too generic and highlights common properties of misclassified compounds. Moreover, the researcher can use CheS-Mapper to inspect how the (Q)SAR model predicts activity cliffs. The CheS-Mapper software is freely available at http://ches-mapper.org.

Model Evaluation Based on the Distribution of Estimated Absolute Prediction Error

The construction of a reliable, practically useful prediction rule for future response is heavily dependent on the "adequacy" of the fitted regression model. In this article, we consider the absolute prediction error, the expected value of the absolute difference between the future and predicted responses, as the model evaluation criterion. This prediction error is easier to interpret than the average squared error and is equivalent to the mis-classification error for the binary outcome. We show that the distributions of the apparent error and its cross-validation counterparts are approximately normal even under a misspecified fitted model. When the prediction rule is "unsmooth", the variance of the above normal distribution can be estimated well via a perturbation-resampling method. We also show how to approximate the distribution of the difference of the estimated prediction errors from two competing models. With two real examples, we demonstrate that the resulting interval estimates for prediction errors provide much more information about model adequacy than the point estimates alone.

Energy/power consumption model for an embedded processor board

This dissertation, whose research has been conducted at the Group of Electronic and Microelectronic Design (GDEM) within the framework of the project Power Consumption Control in Multimedia Terminals (PCCMUTE), focuses on the development of an energy estimation model for the battery-powered embedded processor board. The main objectives and contributions of the work are summarized as follows: A model is proposed to obtain the accurate energy estimation results based on the linear correlation between the performance monitoring counters (PMCs) and energy consumption. the uniqueness of the appropriate PMCs for each different system, the modeling methodology is improved to obtain stable accuracies with slight variations among multiple scenarios and to be repeatable in other systems. It includes two steps: the former, the PMC-filter, to identify the most proper set among the available PMCs of a system and the latter, the k-fold cross validation method, to avoid the bias during the model training stage. The methodology is implemented on a commercial embedded board running the 2.6.34 Linux kernel and the PAPI, a cross-platform interface to configure and access PMCs. The results show that the methodology is able to keep a good stability in different scenarios and provide robust estimation results with the average relative error being less than 5%. Este trabajo fin de máster, cuya investigación se ha desarrollado en el Grupo de Diseño Electrónico y Microelectrónico (GDEM) en el marco del proyecto PccMuTe, se centra en el desarrollo de un modelo de estimación de energía para un sistema empotrado alimentado por batería. Los objetivos principales y las contribuciones de esta tesis se resumen como sigue: Se propone un modelo para obtener estimaciones precisas del consumo de energía de un sistema empotrado. El modelo se basa en la correlación lineal entre los valores de los contadores de prestaciones y el consumo de energía. Considerando la particularidad de los contadores de prestaciones en cada sistema, la metodología de modelado se ha mejorado para obtener precisiones estables, con ligeras variaciones entre escenarios múltiples y para replicar los resultados en diferentes sistemas. La metodología incluye dos etapas: la primera, filtrado-PMC, que consiste en identificar el conjunto más apropiado de contadores de prestaciones de entre los disponibles en un sistema y la segunda, el método de validación cruzada de K iteraciones, cuyo fin es evitar los sesgos durante la fase de entrenamiento. La metodología se implementa en un sistema empotrado que ejecuta el kernel 2.6.34 de Linux y PAPI, un interfaz multiplataforma para configurar y acceder a los contadores. Los resultados muestran que esta metodología consigue una buena estabilidad en diferentes escenarios y proporciona unos resultados robustos de estimación con un error medio relativo inferior al 5%.

Relevance of the glottal pulse and the vocal tract in gender detection

Gender detection is a very important objective to improve efficiency in tasks as speech or speaker recognition, among others. Traditionally gender detection has been focused on fundamental frequency (f0) and cepstral features derived from voiced segments of speech. The methodology presented here consists in obtaining uncorrelated glottal and vocal tract components which are parameterized as mel-frequency coefficients. K-fold and cross-validation using QDA and GMM classifiers showed that better detection rates are reached when glottal source and vocal tract parameters are used in a gender-balanced database of running speech from 340 speakers.

Inteligencia artificial para la predicción y control del acabado superficial en procesos de fresado a alta velocidad

El objetivo principal de esta tesis doctoral es profundizar en el análisis y diseño de un sistema inteligente para la predicción y control del acabado superficial en un proceso de fresado a alta velocidad, basado fundamentalmente en clasificadores Bayesianos, con el prop´osito de desarrollar una metodolog´ıa que facilite el diseño de este tipo de sistemas. El sistema, cuyo propósito es posibilitar la predicción y control de la rugosidad superficial, se compone de un modelo aprendido a partir de datos experimentales con redes Bayesianas, que ayudar´a a comprender los procesos dinámicos involucrados en el mecanizado y las interacciones entre las variables relevantes. Dado que las redes neuronales artificiales son modelos ampliamente utilizados en procesos de corte de materiales, también se incluye un modelo para fresado usándolas, donde se introdujo la geometría y la dureza del material como variables novedosas hasta ahora no estudiadas en este contexto. Por lo tanto, una importante contribución en esta tesis son estos dos modelos para la predicción de la rugosidad superficial, que se comparan con respecto a diferentes aspectos: la influencia de las nuevas variables, los indicadores de evaluación del desempeño, interpretabilidad. Uno de los principales problemas en la modelización con clasificadores Bayesianos es la comprensión de las enormes tablas de probabilidad a posteriori producidas. Introducimos un m´etodo de explicación que genera un conjunto de reglas obtenidas de árboles de decisión. Estos árboles son inducidos a partir de un conjunto de datos simulados generados de las probabilidades a posteriori de la variable clase, calculadas con la red Bayesiana aprendida a partir de un conjunto de datos de entrenamiento. Por último, contribuimos en el campo multiobjetivo en el caso de que algunos de los objetivos no se puedan cuantificar en números reales, sino como funciones en intervalo de valores. Esto ocurre a menudo en aplicaciones de aprendizaje automático, especialmente las basadas en clasificación supervisada. En concreto, se extienden las ideas de dominancia y frontera de Pareto a esta situación. Su aplicación a los estudios de predicción de la rugosidad superficial en el caso de maximizar al mismo tiempo la sensibilidad y la especificidad del clasificador inducido de la red Bayesiana, y no solo maximizar la tasa de clasificación correcta. Los intervalos de estos dos objetivos provienen de un m´etodo de estimación honesta de ambos objetivos, como e.g. validación cruzada en k rodajas o bootstrap.---ABSTRACT---The main objective of this PhD Thesis is to go more deeply into the analysis and design of an intelligent system for surface roughness prediction and control in the end-milling machining process, based fundamentally on Bayesian network classifiers, with the aim of developing a methodology that makes easier the design of this type of systems. The system, whose purpose is to make possible the surface roughness prediction and control, consists of a model learnt from experimental data with the aid of Bayesian networks, that will help to understand the dynamic processes involved in the machining and the interactions among the relevant variables. Since artificial neural networks are models widely used in material cutting proceses, we include also an end-milling model using them, where the geometry and hardness of the piecework are introduced as novel variables not studied so far within this context. Thus, an important contribution in this thesis is these two models for surface roughness prediction, that are then compared with respecto to different aspects: influence of the new variables, performance evaluation metrics, interpretability. One of the main problems with Bayesian classifier-based modelling is the understanding of the enormous posterior probabilitiy tables produced. We introduce an explanation method that generates a set of rules obtained from decision trees. Such trees are induced from a simulated data set generated from the posterior probabilities of the class variable, calculated with the Bayesian network learned from a training data set. Finally, we contribute in the multi-objective field in the case that some of the objectives cannot be quantified as real numbers but as interval-valued functions. This often occurs in machine learning applications, especially those based on supervised classification. Specifically, the dominance and Pareto front ideas are extended to this setting. Its application to the surface roughness prediction studies the case of maximizing simultaneously the sensitivity and specificity of the induced Bayesian network classifier, rather than only maximizing the correct classification rate. Intervals in these two objectives come from a honest estimation method of both objectives, like e.g. k-fold cross-validation or bootstrap.

Screening Subclinical Keratoconus With Placido-Based Corneal Indices

Purpose. To assess in a sample of normal, keratoconic, and keratoconus (KC) suspect eyes the performance of a set of new topographic indices computed directly from the digitized images of the Placido rings. Methods. This comparative study was composed of a total of 124 eyes of 106 patients from the ophthalmic clinics Vissum Alicante and Vissum Almería (Spain) divided into three groups: control group (50 eyes), KC group (50 eyes), and KC suspect group (24 eyes). In all cases, a comprehensive examination was performed, including the corneal topography with a Placidobased CSO topography system. Clinical outcomes were compared among groups, along with the discriminating performance of the proposed irregularity indices. Results. Significant differences at level 0.05 were found on the values of the indices among groups by means of Mann-Whitney-Wilcoxon nonparametric test and Fisher exact test. Additional statistical methods, such as receiver operating characteristic analysis and K-fold cross validation, confirmed the capability of the indices to discriminate between the three groups. Conclusions. Direct analysis of the digitized images of the Placido mires projected on the cornea is a valid and effective tool for detection of corneal irregularities. Although based only on the data from the anterior surface of the cornea, the new indices performed well even when applied to the KC suspect eyes. They have the advantage of simplicity of calculation combined with high sensitivity in corneal irregularity detection and thus can be used as supplementary criteria for diagnosing and grading KC that can be added to the current keratometric classifications.

Canonical solution groups of a homomorphism : manipulator kinematics, nonparametric regression and distributed object systems

The kinematic mapping of a rigid open-link manipulator is a homomorphism between Lie groups. The homomorphisrn has solution groups that act on an inverse kinematic solution element. A canonical representation of solution group operators that act on a solution element of three and seven degree-of-freedom (do!) dextrous manipulators is determined by geometric analysis. Seven canonical solution groups are determined for the seven do! Robotics Research K-1207 and Hollerbach arms. The solution element of a dextrous manipulator is a collection of trivial fibre bundles with solution fibres homotopic to the Torus. If fibre solutions are parameterised by a scalar, a direct inverse funct.ion that maps the scalar and Cartesian base space coordinates to solution element fibre coordinates may be defined. A direct inverse pararneterisation of a solution element may be approximated by a local linear map generated by an inverse augmented Jacobian correction of a linear interpolation. The action of canonical solution group operators on a local linear approximation of the solution element of inverse kinematics of dextrous manipulators generates cyclical solutions. The solution representation is proposed as a model of inverse kinematic transformations in primate nervous systems. Simultaneous calibration of a composition of stereo-camera and manipulator kinematic models is under-determined by equi-output parameter groups in the composition of stereo-camera and Denavit Hartenberg (DH) rnodels. An error measure for simultaneous calibration of a composition of models is derived and parameter subsets with no equi-output groups are determined by numerical experiments to simultaneously calibrate the composition of homogeneous or pan-tilt stereo-camera with DH models. For acceleration of exact Newton second-order re-calibration of DH parameters after a sequential calibration of stereo-camera and DH parameters, an optimal numerical evaluation of DH matrix first order and second order error derivatives with respect to a re-calibration error function is derived, implemented and tested. A distributed object environment for point and click image-based tele-command of manipulators and stereo-cameras is specified and implemented that supports rapid prototyping of numerical experiments in distributed system control. The environment is validated by a hierarchical k-fold cross validated calibration to Cartesian space of a radial basis function regression correction of an affine stereo model. Basic design and performance requirements are defined for scalable virtual micro-kernels that broker inter-Java-virtual-machine remote method invocations between components of secure manageable fault-tolerant open distributed agile Total Quality Managed ISO 9000+ conformant Just in Time manufacturing systems.

A web processing service for validating interpolation

An interoperable web processing service (WPS) for the automatic interpolation of environmental data has been developed in the frame of the INTAMAP project. In order to assess the performance of the interpolation method implemented, a validation WPS has also been developed. This validation WPS can be used to perform leave one out and K-fold cross validation: a full dataset is submitted and a range of validation statistics and diagnostic plots (e.g. histograms, variogram of residuals, mean errors) is received in return. This paper presents the architecture of the validation WPS and a case study is used to briefly illustrate its use in practice. We conclude with a discussion on the current limitations of the system and make proposals for further developments.

Chlorine contribution to quantitative structure and activity relationship models of disinfection by -products' quantum chemical descriptors and toxicities

Quantitative Structure-Activity Relationship (QSAR) has been applied extensively in predicting toxicity of Disinfection By-Products (DBPs) in drinking water. Among many toxicological properties, acute and chronic toxicities of DBPs have been widely used in health risk assessment of DBPs. These toxicities are correlated with molecular properties, which are usually correlated with molecular descriptors. The primary goals of this thesis are: (1) to investigate the effects of molecular descriptors (e.g., chlorine number) on molecular properties such as energy of the lowest unoccupied molecular orbital (E LUMO) via QSAR modelling and analysis; (2) to validate the models by using internal and external cross-validation techniques; (3) to quantify the model uncertainties through Taylor and Monte Carlo Simulation. One of the very important ways to predict molecular properties such as ELUMO is using QSAR analysis. In this study, number of chlorine (NCl ) and number of carbon (NC) as well as energy of the highest occupied molecular orbital (EHOMO) are used as molecular descriptors. There are typically three approaches used in QSAR model development: (1) Linear or Multi-linear Regression (MLR); (2) Partial Least Squares (PLS); and (3) Principle Component Regression (PCR). In QSAR analysis, a very critical step is model validation after QSAR models are established and before applying them to toxicity prediction. The DBPs to be studied include five chemical classes: chlorinated alkanes, alkenes, and aromatics. In addition, validated QSARs are developed to describe the toxicity of selected groups (i.e., chloro-alkane and aromatic compounds with a nitro- or cyano group) of DBP chemicals to three types of organisms (e.g., Fish, T. pyriformis, and P.pyosphoreum) based on experimental toxicity data from the literature. The results show that: (1) QSAR models to predict molecular property built by MLR, PLS or PCR can be used either to select valid data points or to eliminate outliers; (2) The Leave-One-Out Cross-Validation procedure by itself is not enough to give a reliable representation of the predictive ability of the QSAR models, however, Leave-Many-Out/K-fold cross-validation and external validation can be applied together to achieve more reliable results; (3) E LUMO are shown to correlate highly with the NCl for several classes of DBPs; and (4) According to uncertainty analysis using Taylor method, the uncertainty of QSAR models is contributed mostly from NCl for all DBP classes.

Chlorine Contribution to Quantitative Structure and Activity Relationship Models of Disinfection By-Products' Quantum Chemical Descriptors and Toxicities

Quantitative Structure-Activity Relationship (QSAR) has been applied extensively in predicting toxicity of Disinfection By-Products (DBPs) in drinking water. Among many toxicological properties, acute and chronic toxicities of DBPs have been widely used in health risk assessment of DBPs. These toxicities are correlated with molecular properties, which are usually correlated with molecular descriptors. The primary goals of this thesis are: 1) to investigate the effects of molecular descriptors (e.g., chlorine number) on molecular properties such as energy of the lowest unoccupied molecular orbital (ELUMO) via QSAR modelling and analysis; 2) to validate the models by using internal and external cross-validation techniques; 3) to quantify the model uncertainties through Taylor and Monte Carlo Simulation. One of the very important ways to predict molecular properties such as ELUMO is using QSAR analysis. In this study, number of chlorine (NCl) and number of carbon (NC) as well as energy of the highest occupied molecular orbital (EHOMO) are used as molecular descriptors. There are typically three approaches used in QSAR model development: 1) Linear or Multi-linear Regression (MLR); 2) Partial Least Squares (PLS); and 3) Principle Component Regression (PCR). In QSAR analysis, a very critical step is model validation after QSAR models are established and before applying them to toxicity prediction. The DBPs to be studied include five chemical classes: chlorinated alkanes, alkenes, and aromatics. In addition, validated QSARs are developed to describe the toxicity of selected groups (i.e., chloro-alkane and aromatic compounds with a nitro- or cyano group) of DBP chemicals to three types of organisms (e.g., Fish, T. pyriformis, and P.pyosphoreum) based on experimental toxicity data from the literature. The results show that: 1) QSAR models to predict molecular property built by MLR, PLS or PCR can be used either to select valid data points or to eliminate outliers; 2) The Leave-One-Out Cross-Validation procedure by itself is not enough to give a reliable representation of the predictive ability of the QSAR models, however, Leave-Many-Out/K-fold cross-validation and external validation can be applied together to achieve more reliable results; 3) ELUMO are shown to correlate highly with the NCl for several classes of DBPs; and 4) According to uncertainty analysis using Taylor method, the uncertainty of QSAR models is contributed mostly from NCl for all DBP classes.

METAMATERIAL DEVICE AND USES THEREOF

The present invention relates to a logic gate, comprising a metamaterial surface enhanced Raman scattering (MetaSERS) sensor, comprising (a) alphabetical metamaterials in the form of split ring resonators operating in the wavelength range of from 560 to 2200 nm; and (b) a guanine (G) and thymine (T)-rich oligonucleotide that can, upon presence of potassium cations (K+), fold into a G-quadruplex structure, and in presence of Hg2+, form a T-Hg2+-T hairpin complex that inhibits or disrupts the G-quadruplex structure formed in presence of K+, as well as methods of operating and using such a logic gate.

Tensor Completion for Multidimensional Inverse Problems with Applications to Magnetic Resonance Relaxometry

This thesis deals with tensor completion for the solution of multidimensional inverse problems. We study the problem of reconstructing an approximately low rank tensor from a small number of noisy linear measurements. New recovery guarantees, numerical algorithms, non-uniform sampling strategies, and parameter selection algorithms are developed. We derive a fixed point continuation algorithm for tensor completion and prove its convergence. A restricted isometry property (RIP) based tensor recovery guarantee is proved. Probabilistic recovery guarantees are obtained for sub-Gaussian measurement operators and for measurements obtained by non-uniform sampling from a Parseval tight frame. We show how tensor completion can be used to solve multidimensional inverse problems arising in NMR relaxometry. Algorithms are developed for regularization parameter selection, including accelerated k-fold cross-validation and generalized cross-validation. These methods are validated on experimental and simulated data. We also derive condition number estimates for nonnegative least squares problems. Tensor recovery promises to significantly accelerate N-dimensional NMR relaxometry and related experiments, enabling previously impractical experiments. Our methods could also be applied to other inverse problems arising in machine learning, image processing, signal processing, computer vision, and other fields.