Network-based analysis of genome-wide scans of natural selection

The genomic era brought by recent advances in the next-generation sequencing technology makes the genome-wide scans of natural selection a reality. Currently, almost all the statistical tests and analytical methods for identifying genes under selection was performed on the individual gene basis. Although these methods have the power of identifying gene subject to strong selection, they have limited power in discovering genes targeted by moderate or weak selection forces, which are crucial for understanding the molecular mechanisms of complex phenotypes and diseases. Recent availability and rapid completeness of many gene network and protein-protein interaction databases accompanying the genomic era open the avenues of exploring the possibility of enhancing the power of discovering genes under natural selection. The aim of the thesis is to explore and develop normal mixture model based methods for leveraging gene network information to enhance the power of natural selection target gene discovery. The results show that the developed statistical method, which combines the posterior log odds of the standard normal mixture model and the Guilt-By-Association score of the gene network in a naïve Bayes framework, has the power to discover moderate/weak selection gene which bridges the genes under strong selection and it helps our understanding the biology under complex diseases and related natural selection phenotypes.^

Regularization for sparsity in statistical analysis and machine learning

Pragmatism is the leading motivation of regularization. We can understand regularization as a modification of the maximum-likelihood estimator so that a reasonable answer could be given in an unstable or ill-posed situation. To mention some typical examples, this happens when fitting parametric or non-parametric models with more parameters than data or when estimating large covariance matrices. Regularization is usually used, in addition, to improve the bias-variance tradeoff of an estimation. Then, the definition of regularization is quite general, and, although the introduction of a penalty is probably the most popular type, it is just one out of multiple forms of regularization. In this dissertation, we focus on the applications of regularization for obtaining sparse or parsimonious representations, where only a subset of the inputs is used. A particular form of regularization, L1-regularization, plays a key role for reaching sparsity. Most of the contributions presented here revolve around L1-regularization, although other forms of regularization are explored (also pursuing sparsity in some sense). In addition to present a compact review of L1-regularization and its applications in statistical and machine learning, we devise methodology for regression, supervised classification and structure induction of graphical models. Within the regression paradigm, we focus on kernel smoothing learning, proposing techniques for kernel design that are suitable for high dimensional settings and sparse regression functions. We also present an application of regularized regression techniques for modeling the response of biological neurons. Supervised classification advances deal, on the one hand, with the application of regularization for obtaining a na¨ıve Bayes classifier and, on the other hand, with a novel algorithm for brain-computer interface design that uses group regularization in an efficient manner. Finally, we present a heuristic for inducing structures of Gaussian Bayesian networks using L1-regularization as a filter. El pragmatismo es la principal motivación de la regularización. Podemos entender la regularización como una modificación del estimador de máxima verosimilitud, de tal manera que se pueda dar una respuesta cuando la configuración del problema es inestable. A modo de ejemplo, podemos mencionar el ajuste de modelos paramétricos o no paramétricos cuando hay más parámetros que casos en el conjunto de datos, o la estimación de grandes matrices de covarianzas. Se suele recurrir a la regularización, además, para mejorar el compromiso sesgo-varianza en una estimación. Por tanto, la definición de regularización es muy general y, aunque la introducción de una función de penalización es probablemente el método más popular, éste es sólo uno de entre varias posibilidades. En esta tesis se ha trabajado en aplicaciones de regularización para obtener representaciones dispersas, donde sólo se usa un subconjunto de las entradas. En particular, la regularización L1 juega un papel clave en la búsqueda de dicha dispersión. La mayor parte de las contribuciones presentadas en la tesis giran alrededor de la regularización L1, aunque también se exploran otras formas de regularización (que igualmente persiguen un modelo disperso). Además de presentar una revisión de la regularización L1 y sus aplicaciones en estadística y aprendizaje de máquina, se ha desarrollado metodología para regresión, clasificación supervisada y aprendizaje de estructura en modelos gráficos. Dentro de la regresión, se ha trabajado principalmente en métodos de regresión local, proponiendo técnicas de diseño del kernel que sean adecuadas a configuraciones de alta dimensionalidad y funciones de regresión dispersas. También se presenta una aplicación de las técnicas de regresión regularizada para modelar la respuesta de neuronas reales. Los avances en clasificación supervisada tratan, por una parte, con el uso de regularización para obtener un clasificador naive Bayes y, por otra parte, con el desarrollo de un algoritmo que usa regularización por grupos de una manera eficiente y que se ha aplicado al diseño de interfaces cerebromáquina. Finalmente, se presenta una heurística para inducir la estructura de redes Bayesianas Gaussianas usando regularización L1 a modo de filtro.

Contributions to Bayesian network learning with applications to neuroscience

Neuronal morphology is a key feature in the study of brain circuits, as it is highly related to information processing and functional identification. Neuronal morphology affects the process of integration of inputs from other neurons and determines the neurons which receive the output of the neurons. Different parts of the neurons can operate semi-independently according to the spatial location of the synaptic connections. As a result, there is considerable interest in the analysis of the microanatomy of nervous cells since it constitutes an excellent tool for better understanding cortical function. However, the morphologies, molecular features and electrophysiological properties of neuronal cells are extremely variable. Except for some special cases, this variability makes it hard to find a set of features that unambiguously define a neuronal type. In addition, there are distinct types of neurons in particular regions of the brain. This morphological variability makes the analysis and modeling of neuronal morphology a challenge. Uncertainty is a key feature in many complex real-world problems. Probability theory provides a framework for modeling and reasoning with uncertainty. Probabilistic graphical models combine statistical theory and graph theory to provide a tool for managing domains with uncertainty. In particular, we focus on Bayesian networks, the most commonly used probabilistic graphical model. In this dissertation, we design new methods for learning Bayesian networks and apply them to the problem of modeling and analyzing morphological data from neurons. The morphology of a neuron can be quantified using a number of measurements, e.g., the length of the dendrites and the axon, the number of bifurcations, the direction of the dendrites and the axon, etc. These measurements can be modeled as discrete or continuous data. The continuous data can be linear (e.g., the length or the width of a dendrite) or directional (e.g., the direction of the axon). These data may follow complex probability distributions and may not fit any known parametric distribution. Modeling this kind of problems using hybrid Bayesian networks with discrete, linear and directional variables poses a number of challenges regarding learning from data, inference, etc. In this dissertation, we propose a method for modeling and simulating basal dendritic trees from pyramidal neurons using Bayesian networks to capture the interactions between the variables in the problem domain. A complete set of variables is measured from the dendrites, and a learning algorithm is applied to find the structure and estimate the parameters of the probability distributions included in the Bayesian networks. Then, a simulation algorithm is used to build the virtual dendrites by sampling values from the Bayesian networks, and a thorough evaluation is performed to show the model’s ability to generate realistic dendrites. In this first approach, the variables are discretized so that discrete Bayesian networks can be learned and simulated. Then, we address the problem of learning hybrid Bayesian networks with different kinds of variables. Mixtures of polynomials have been proposed as a way of representing probability densities in hybrid Bayesian networks. We present a method for learning mixtures of polynomials approximations of one-dimensional, multidimensional and conditional probability densities from data. The method is based on basis spline interpolation, where a density is approximated as a linear combination of basis splines. The proposed algorithms are evaluated using artificial datasets. We also use the proposed methods as a non-parametric density estimation technique in Bayesian network classifiers. Next, we address the problem of including directional data in Bayesian networks. These data have some special properties that rule out the use of classical statistics. Therefore, different distributions and statistics, such as the univariate von Mises and the multivariate von Mises–Fisher distributions, should be used to deal with this kind of information. In particular, we extend the naive Bayes classifier to the case where the conditional probability distributions of the predictive variables given the class follow either of these distributions. We consider the simple scenario, where only directional predictive variables are used, and the hybrid case, where discrete, Gaussian and directional distributions are mixed. The classifier decision functions and their decision surfaces are studied at length. Artificial examples are used to illustrate the behavior of the classifiers. The proposed classifiers are empirically evaluated over real datasets. We also study the problem of interneuron classification. An extensive group of experts is asked to classify a set of neurons according to their most prominent anatomical features. A web application is developed to retrieve the experts’ classifications. We compute agreement measures to analyze the consensus between the experts when classifying the neurons. Using Bayesian networks and clustering algorithms on the resulting data, we investigate the suitability of the anatomical terms and neuron types commonly used in the literature. Additionally, we apply supervised learning approaches to automatically classify interneurons using the values of their morphological measurements. Then, a methodology for building a model which captures the opinions of all the experts is presented. First, one Bayesian network is learned for each expert, and we propose an algorithm for clustering Bayesian networks corresponding to experts with similar behaviors. Then, a Bayesian network which represents the opinions of each group of experts is induced. Finally, a consensus Bayesian multinet which models the opinions of the whole group of experts is built. A thorough analysis of the consensus model identifies different behaviors between the experts when classifying the interneurons in the experiment. A set of characterizing morphological traits for the neuronal types can be defined by performing inference in the Bayesian multinet. These findings are used to validate the model and to gain some insights into neuron morphology. Finally, we study a classification problem where the true class label of the training instances is not known. Instead, a set of class labels is available for each instance. This is inspired by the neuron classification problem, where a group of experts is asked to individually provide a class label for each instance. We propose a novel approach for learning Bayesian networks using count vectors which represent the number of experts who selected each class label for each instance. These Bayesian networks are evaluated using artificial datasets from supervised learning problems. Resumen La morfología neuronal es una característica clave en el estudio de los circuitos cerebrales, ya que está altamente relacionada con el procesado de información y con los roles funcionales. La morfología neuronal afecta al proceso de integración de las señales de entrada y determina las neuronas que reciben las salidas de otras neuronas. Las diferentes partes de la neurona pueden operar de forma semi-independiente de acuerdo a la localización espacial de las conexiones sinápticas. Por tanto, existe un interés considerable en el análisis de la microanatomía de las células nerviosas, ya que constituye una excelente herramienta para comprender mejor el funcionamiento de la corteza cerebral. Sin embargo, las propiedades morfológicas, moleculares y electrofisiológicas de las células neuronales son extremadamente variables. Excepto en algunos casos especiales, esta variabilidad morfológica dificulta la definición de un conjunto de características que distingan claramente un tipo neuronal. Además, existen diferentes tipos de neuronas en regiones particulares del cerebro. La variabilidad neuronal hace que el análisis y el modelado de la morfología neuronal sean un importante reto científico. La incertidumbre es una propiedad clave en muchos problemas reales. La teoría de la probabilidad proporciona un marco para modelar y razonar bajo incertidumbre. Los modelos gráficos probabilísticos combinan la teoría estadística y la teoría de grafos con el objetivo de proporcionar una herramienta con la que trabajar bajo incertidumbre. En particular, nos centraremos en las redes bayesianas, el modelo más utilizado dentro de los modelos gráficos probabilísticos. En esta tesis hemos diseñado nuevos métodos para aprender redes bayesianas, inspirados por y aplicados al problema del modelado y análisis de datos morfológicos de neuronas. La morfología de una neurona puede ser cuantificada usando una serie de medidas, por ejemplo, la longitud de las dendritas y el axón, el número de bifurcaciones, la dirección de las dendritas y el axón, etc. Estas medidas pueden ser modeladas como datos continuos o discretos. A su vez, los datos continuos pueden ser lineales (por ejemplo, la longitud o la anchura de una dendrita) o direccionales (por ejemplo, la dirección del axón). Estos datos pueden llegar a seguir distribuciones de probabilidad muy complejas y pueden no ajustarse a ninguna distribución paramétrica conocida. El modelado de este tipo de problemas con redes bayesianas híbridas incluyendo variables discretas, lineales y direccionales presenta una serie de retos en relación al aprendizaje a partir de datos, la inferencia, etc. En esta tesis se propone un método para modelar y simular árboles dendríticos basales de neuronas piramidales usando redes bayesianas para capturar las interacciones entre las variables del problema. Para ello, se mide un amplio conjunto de variables de las dendritas y se aplica un algoritmo de aprendizaje con el que se aprende la estructura y se estiman los parámetros de las distribuciones de probabilidad que constituyen las redes bayesianas. Después, se usa un algoritmo de simulación para construir dendritas virtuales mediante el muestreo de valores de las redes bayesianas. Finalmente, se lleva a cabo una profunda evaluaci ón para verificar la capacidad del modelo a la hora de generar dendritas realistas. En esta primera aproximación, las variables fueron discretizadas para poder aprender y muestrear las redes bayesianas. A continuación, se aborda el problema del aprendizaje de redes bayesianas con diferentes tipos de variables. Las mixturas de polinomios constituyen un método para representar densidades de probabilidad en redes bayesianas híbridas. Presentamos un método para aprender aproximaciones de densidades unidimensionales, multidimensionales y condicionales a partir de datos utilizando mixturas de polinomios. El método se basa en interpolación con splines, que aproxima una densidad como una combinación lineal de splines. Los algoritmos propuestos se evalúan utilizando bases de datos artificiales. Además, las mixturas de polinomios son utilizadas como un método no paramétrico de estimación de densidades para clasificadores basados en redes bayesianas. Después, se estudia el problema de incluir información direccional en redes bayesianas. Este tipo de datos presenta una serie de características especiales que impiden el uso de las técnicas estadísticas clásicas. Por ello, para manejar este tipo de información se deben usar estadísticos y distribuciones de probabilidad específicos, como la distribución univariante von Mises y la distribución multivariante von Mises–Fisher. En concreto, en esta tesis extendemos el clasificador naive Bayes al caso en el que las distribuciones de probabilidad condicionada de las variables predictoras dada la clase siguen alguna de estas distribuciones. Se estudia el caso base, en el que sólo se utilizan variables direccionales, y el caso híbrido, en el que variables discretas, lineales y direccionales aparecen mezcladas. También se estudian los clasificadores desde un punto de vista teórico, derivando sus funciones de decisión y las superficies de decisión asociadas. El comportamiento de los clasificadores se ilustra utilizando bases de datos artificiales. Además, los clasificadores son evaluados empíricamente utilizando bases de datos reales. También se estudia el problema de la clasificación de interneuronas. Desarrollamos una aplicación web que permite a un grupo de expertos clasificar un conjunto de neuronas de acuerdo a sus características morfológicas más destacadas. Se utilizan medidas de concordancia para analizar el consenso entre los expertos a la hora de clasificar las neuronas. Se investiga la idoneidad de los términos anatómicos y de los tipos neuronales utilizados frecuentemente en la literatura a través del análisis de redes bayesianas y la aplicación de algoritmos de clustering. Además, se aplican técnicas de aprendizaje supervisado con el objetivo de clasificar de forma automática las interneuronas a partir de sus valores morfológicos. A continuación, se presenta una metodología para construir un modelo que captura las opiniones de todos los expertos. Primero, se genera una red bayesiana para cada experto y se propone un algoritmo para agrupar las redes bayesianas que se corresponden con expertos con comportamientos similares. Después, se induce una red bayesiana que modela la opinión de cada grupo de expertos. Por último, se construye una multired bayesiana que modela las opiniones del conjunto completo de expertos. El análisis del modelo consensuado permite identificar diferentes comportamientos entre los expertos a la hora de clasificar las neuronas. Además, permite extraer un conjunto de características morfológicas relevantes para cada uno de los tipos neuronales mediante inferencia con la multired bayesiana. Estos descubrimientos se utilizan para validar el modelo y constituyen información relevante acerca de la morfología neuronal. Por último, se estudia un problema de clasificación en el que la etiqueta de clase de los datos de entrenamiento es incierta. En cambio, disponemos de un conjunto de etiquetas para cada instancia. Este problema está inspirado en el problema de la clasificación de neuronas, en el que un grupo de expertos proporciona una etiqueta de clase para cada instancia de manera individual. Se propone un método para aprender redes bayesianas utilizando vectores de cuentas, que representan el número de expertos que seleccionan cada etiqueta de clase para cada instancia. Estas redes bayesianas se evalúan utilizando bases de datos artificiales de problemas de aprendizaje supervisado.

Multi-dimensional classification using Bayesian networks for stationary and evolving streaming data

Hoy en día, con la evolución continua y rápida de las tecnologías de la información y los dispositivos de computación, se recogen y almacenan continuamente grandes volúmenes de datos en distintos dominios y a través de diversas aplicaciones del mundo real. La extracción de conocimiento útil de una cantidad tan enorme de datos no se puede realizar habitualmente de forma manual, y requiere el uso de técnicas adecuadas de aprendizaje automático y de minería de datos. La clasificación es una de las técnicas más importantes que ha sido aplicada con éxito a varias áreas. En general, la clasificación se compone de dos pasos principales: en primer lugar, aprender un modelo de clasificación o clasificador a partir de un conjunto de datos de entrenamiento, y en segundo lugar, clasificar las nuevas instancias de datos utilizando el clasificador aprendido. La clasificación es supervisada cuando todas las etiquetas están presentes en los datos de entrenamiento (es decir, datos completamente etiquetados), semi-supervisada cuando sólo algunas etiquetas son conocidas (es decir, datos parcialmente etiquetados), y no supervisada cuando todas las etiquetas están ausentes en los datos de entrenamiento (es decir, datos no etiquetados). Además, aparte de esta taxonomía, el problema de clasificación se puede categorizar en unidimensional o multidimensional en función del número de variables clase, una o más, respectivamente; o también puede ser categorizado en estacionario o cambiante con el tiempo en función de las características de los datos y de la tasa de cambio subyacente. A lo largo de esta tesis, tratamos el problema de clasificación desde tres perspectivas diferentes, a saber, clasificación supervisada multidimensional estacionaria, clasificación semisupervisada unidimensional cambiante con el tiempo, y clasificación supervisada multidimensional cambiante con el tiempo. Para llevar a cabo esta tarea, hemos usado básicamente los clasificadores Bayesianos como modelos. La primera contribución, dirigiéndose al problema de clasificación supervisada multidimensional estacionaria, se compone de dos nuevos métodos de aprendizaje de clasificadores Bayesianos multidimensionales a partir de datos estacionarios. Los métodos se proponen desde dos puntos de vista diferentes. El primer método, denominado CB-MBC, se basa en una estrategia de envoltura de selección de variables que es voraz y hacia delante, mientras que el segundo, denominado MB-MBC, es una estrategia de filtrado de variables con una aproximación basada en restricciones y en el manto de Markov. Ambos métodos han sido aplicados a dos problemas reales importantes, a saber, la predicción de los inhibidores de la transcriptasa inversa y de la proteasa para el problema de infección por el virus de la inmunodeficiencia humana tipo 1 (HIV-1), y la predicción del European Quality of Life-5 Dimensions (EQ-5D) a partir de los cuestionarios de la enfermedad de Parkinson con 39 ítems (PDQ-39). El estudio experimental incluye comparaciones de CB-MBC y MB-MBC con los métodos del estado del arte de la clasificación multidimensional, así como con métodos comúnmente utilizados para resolver el problema de predicción de la enfermedad de Parkinson, a saber, la regresión logística multinomial, mínimos cuadrados ordinarios, y mínimas desviaciones absolutas censuradas. En ambas aplicaciones, los resultados han sido prometedores con respecto a la precisión de la clasificación, así como en relación al análisis de las estructuras gráficas que identifican interacciones conocidas y novedosas entre las variables. La segunda contribución, referida al problema de clasificación semi-supervisada unidimensional cambiante con el tiempo, consiste en un método nuevo (CPL-DS) para clasificar flujos de datos parcialmente etiquetados. Los flujos de datos difieren de los conjuntos de datos estacionarios en su proceso de generación muy rápido y en su aspecto de cambio de concepto. Es decir, los conceptos aprendidos y/o la distribución subyacente están probablemente cambiando y evolucionando en el tiempo, lo que hace que el modelo de clasificación actual sea obsoleto y deba ser actualizado. CPL-DS utiliza la divergencia de Kullback-Leibler y el método de bootstrapping para cuantificar y detectar tres tipos posibles de cambio: en las predictoras, en la a posteriori de la clase o en ambas. Después, si se detecta cualquier cambio, un nuevo modelo de clasificación se aprende usando el algoritmo EM; si no, el modelo de clasificación actual se mantiene sin modificaciones. CPL-DS es general, ya que puede ser aplicado a varios modelos de clasificación. Usando dos modelos diferentes, el clasificador naive Bayes y la regresión logística, CPL-DS se ha probado con flujos de datos sintéticos y también se ha aplicado al problema real de la detección de código malware, en el cual los nuevos ficheros recibidos deben ser continuamente clasificados en malware o goodware. Los resultados experimentales muestran que nuestro método es efectivo para la detección de diferentes tipos de cambio a partir de los flujos de datos parcialmente etiquetados y también tiene una buena precisión de la clasificación. Finalmente, la tercera contribución, sobre el problema de clasificación supervisada multidimensional cambiante con el tiempo, consiste en dos métodos adaptativos, a saber, Locally Adpative-MB-MBC (LA-MB-MBC) y Globally Adpative-MB-MBC (GA-MB-MBC). Ambos métodos monitorizan el cambio de concepto a lo largo del tiempo utilizando la log-verosimilitud media como métrica y el test de Page-Hinkley. Luego, si se detecta un cambio de concepto, LA-MB-MBC adapta el actual clasificador Bayesiano multidimensional localmente alrededor de cada nodo cambiado, mientras que GA-MB-MBC aprende un nuevo clasificador Bayesiano multidimensional. El estudio experimental realizado usando flujos de datos sintéticos multidimensionales indica los méritos de los métodos adaptativos propuestos. ABSTRACT Nowadays, with the ongoing and rapid evolution of information technology and computing devices, large volumes of data are continuously collected and stored in different domains and through various real-world applications. Extracting useful knowledge from such a huge amount of data usually cannot be performed manually, and requires the use of adequate machine learning and data mining techniques. Classification is one of the most important techniques that has been successfully applied to several areas. Roughly speaking, classification consists of two main steps: first, learn a classification model or classifier from an available training data, and secondly, classify the new incoming unseen data instances using the learned classifier. Classification is supervised when the whole class values are present in the training data (i.e., fully labeled data), semi-supervised when only some class values are known (i.e., partially labeled data), and unsupervised when the whole class values are missing in the training data (i.e., unlabeled data). In addition, besides this taxonomy, the classification problem can be categorized into uni-dimensional or multi-dimensional depending on the number of class variables, one or more, respectively; or can be also categorized into stationary or streaming depending on the characteristics of the data and the rate of change underlying it. Through this thesis, we deal with the classification problem under three different settings, namely, supervised multi-dimensional stationary classification, semi-supervised unidimensional streaming classification, and supervised multi-dimensional streaming classification. To accomplish this task, we basically used Bayesian network classifiers as models. The first contribution, addressing the supervised multi-dimensional stationary classification problem, consists of two new methods for learning multi-dimensional Bayesian network classifiers from stationary data. They are proposed from two different points of view. The first method, named CB-MBC, is based on a wrapper greedy forward selection approach, while the second one, named MB-MBC, is a filter constraint-based approach based on Markov blankets. Both methods are applied to two important real-world problems, namely, the prediction of the human immunodeficiency virus type 1 (HIV-1) reverse transcriptase and protease inhibitors, and the prediction of the European Quality of Life-5 Dimensions (EQ-5D) from 39-item Parkinson’s Disease Questionnaire (PDQ-39). The experimental study includes comparisons of CB-MBC and MB-MBC against state-of-the-art multi-dimensional classification methods, as well as against commonly used methods for solving the Parkinson’s disease prediction problem, namely, multinomial logistic regression, ordinary least squares, and censored least absolute deviations. For both considered case studies, results are promising in terms of classification accuracy as well as regarding the analysis of the learned MBC graphical structures identifying known and novel interactions among variables. The second contribution, addressing the semi-supervised uni-dimensional streaming classification problem, consists of a novel method (CPL-DS) for classifying partially labeled data streams. Data streams differ from the stationary data sets by their highly rapid generation process and their concept-drifting aspect. That is, the learned concepts and/or the underlying distribution are likely changing and evolving over time, which makes the current classification model out-of-date requiring to be updated. CPL-DS uses the Kullback-Leibler divergence and bootstrapping method to quantify and detect three possible kinds of drift: feature, conditional or dual. Then, if any occurs, a new classification model is learned using the expectation-maximization algorithm; otherwise, the current classification model is kept unchanged. CPL-DS is general as it can be applied to several classification models. Using two different models, namely, naive Bayes classifier and logistic regression, CPL-DS is tested with synthetic data streams and applied to the real-world problem of malware detection, where the new received files should be continuously classified into malware or goodware. Experimental results show that our approach is effective for detecting different kinds of drift from partially labeled data streams, as well as having a good classification performance. Finally, the third contribution, addressing the supervised multi-dimensional streaming classification problem, consists of two adaptive methods, namely, Locally Adaptive-MB-MBC (LA-MB-MBC) and Globally Adaptive-MB-MBC (GA-MB-MBC). Both methods monitor the concept drift over time using the average log-likelihood score and the Page-Hinkley test. Then, if a drift is detected, LA-MB-MBC adapts the current multi-dimensional Bayesian network classifier locally around each changed node, whereas GA-MB-MBC learns a new multi-dimensional Bayesian network classifier from scratch. Experimental study carried out using synthetic multi-dimensional data streams shows the merits of both proposed adaptive methods.

AllerTOP v.2 - a server for in silico prediction of allergens

Allergy is an overreaction by the immune system to a previously encountered, ordinarily harmless substance - typically proteins - resulting in skin rash, swelling of mucous membranes, sneezing or wheezing, or other abnormal conditions. The use of modified proteins is increasingly widespread: their presence in food, commercial products, such as washing powder, and medical therapeutics and diagnostics, makes predicting and identifying potential allergens a crucial societal issue. The prediction of allergens has been explored widely using bioinformatics, with many tools being developed in the last decade; many of these are freely available online. Here, we report a set of novel models for allergen prediction utilizing amino acid E-descriptors, auto- and cross-covariance transformation, and several machine learning methods for classification, including logistic regression (LR), decision tree (DT), naïve Bayes (NB), random forest (RF), multilayer perceptron (MLP) and k nearest neighbours (kNN). The best performing method was kNN with 85.3% accuracy at 5-fold cross-validation. The resulting model has been implemented in a revised version of the AllerTOP server (http://www.ddg-pharmfac.net/AllerTOP). © Springer-Verlag 2014.

AllerTOP - a server for in silico prediction of allergens

Background: Allergy is a form of hypersensitivity to normally innocuous substances, such as dust, pollen, foods or drugs. Allergens are small antigens that commonly provoke an IgE antibody response. There are two types of bioinformatics-based allergen prediction. The first approach follows FAO/WHO Codex alimentarius guidelines and searches for sequence similarity. The second approach is based on identifying conserved allergenicity-related linear motifs. Both approaches assume that allergenicity is a linearly coded property. In the present study, we applied ACC pre-processing to sets of known allergens, developing alignment-independent models for allergen recognition based on the main chemical properties of amino acid sequences.Results: A set of 684 food, 1,156 inhalant and 555 toxin allergens was collected from several databases. A set of non-allergens from the same species were selected to mirror the allergen set. The amino acids in the protein sequences were described by three z-descriptors (z1, z2 and z3) and by auto- and cross-covariance (ACC) transformation were converted into uniform vectors. Each protein was presented as a vector of 45 variables. Five machine learning methods for classification were applied in the study to derive models for allergen prediction. The methods were: discriminant analysis by partial least squares (DA-PLS), logistic regression (LR), decision tree (DT), naïve Bayes (NB) and k nearest neighbours (kNN). The best performing model was derived by kNN at k = 3. It was optimized, cross-validated and implemented in a server named AllerTOP, freely accessible at http://www.pharmfac.net/allertop. AllerTOP also predicts the most probable route of exposure. In comparison to other servers for allergen prediction, AllerTOP outperforms them with 94% sensitivity.Conclusions: AllerTOP is the first alignment-free server for in silico prediction of allergens based on the main physicochemical properties of proteins. Significantly, as well allergenicity AllerTOP is able to predict the route of allergen exposure: food, inhalant or toxin. © 2013 Dimitrov et al.; licensee BioMed Central Ltd.

Signal processing of physiological signals for automated assessment of stress in computer users

The need to provide computers with the ability to distinguish the affective state of their users is a major requirement for the practical implementation of affective computing concepts. This dissertation proposes the application of signal processing methods on physiological signals to extract from them features that can be processed by learning pattern recognition systems to provide cues about a person's affective state. In particular, combining physiological information sensed from a user's left hand in a non-invasive way with the pupil diameter information from an eye-tracking system may provide a computer with an awareness of its user's affective responses in the course of human-computer interactions. In this study an integrated hardware-software setup was developed to achieve automatic assessment of the affective status of a computer user. A computer-based "Paced Stroop Test" was designed as a stimulus to elicit emotional stress in the subject during the experiment. Four signals: the Galvanic Skin Response (GSR), the Blood Volume Pulse (BVP), the Skin Temperature (ST) and the Pupil Diameter (PD), were monitored and analyzed to differentiate affective states in the user. Several signal processing techniques were applied on the collected signals to extract their most relevant features. These features were analyzed with learning classification systems, to accomplish the affective state identification. Three learning algorithms: Naïve Bayes, Decision Tree and Support Vector Machine were applied to this identification process and their levels of classification accuracy were compared. The results achieved indicate that the physiological signals monitored do, in fact, have a strong correlation with the changes in the emotional states of the experimental subjects. These results also revealed that the inclusion of pupil diameter information significantly improved the performance of the emotion recognition system. ^

Statistical methods for polyhedral shape classification with incomplete data - application to cryo-electron tomographic images

A certain type of bacterial inclusion, known as a bacterial microcompartment, was recently identified and imaged through cryo-electron tomography. A reconstructed 3D object from single-axis limited angle tilt-series cryo-electron tomography contains missing regions and this problem is known as the missing wedge problem. Due to missing regions on the reconstructed images, analyzing their 3D structures is a challenging problem. The existing methods overcome this problem by aligning and averaging several similar shaped objects. These schemes work well if the objects are symmetric and several objects with almost similar shapes and sizes are available. Since the bacterial inclusions studied here are not symmetric, are deformed, and show a wide range of shapes and sizes, the existing approaches are not appropriate. This research develops new statistical methods for analyzing geometric properties, such as volume, symmetry, aspect ratio, polyhedral structures etc., of these bacterial inclusions in presence of missing data. These methods work with deformed and non-symmetric varied shaped objects and do not necessitate multiple objects for handling the missing wedge problem. The developed methods and contributions include: (a) an improved method for manual image segmentation, (b) a new approach to 'complete' the segmented and reconstructed incomplete 3D images, (c) a polyhedral structural distance model to predict the polyhedral shapes of these microstructures, (d) a new shape descriptor for polyhedral shapes, named as polyhedron profile statistic, and (e) the Bayes classifier, linear discriminant analysis and support vector machine based classifiers for supervised incomplete polyhedral shape classification. Finally, the predicted 3D shapes for these bacterial microstructures belong to the Johnson solids family, and these shapes along with their other geometric properties are important for better understanding of their chemical and biological characteristics.

Data Mining for Network Intrusion Detection : A comparison of data mining algorithms and an analysis of relevant features for detecting cyber-attacks

Data mining can be defined as the extraction of implicit, previously un-known, and potentially useful information from data. Numerous re-searchers have been developing security technology and exploring new methods to detect cyber-attacks with the DARPA 1998 dataset for Intrusion Detection and the modified versions of this dataset KDDCup99 and NSL-KDD, but until now no one have examined the performance of the Top 10 data mining algorithms selected by experts in data mining. The compared classification learning algorithms in this thesis are: C4.5, CART, k-NN and Naïve Bayes. The performance of these algorithms are compared with accuracy, error rate and average cost on modified versions of NSL-KDD train and test dataset where the instances are classified into normal and four cyber-attack categories: DoS, Probing, R2L and U2R. Additionally the most important features to detect cyber-attacks in all categories and in each category are evaluated with Weka’s Attribute Evaluator and ranked according to Information Gain. The results show that the classification algorithm with best performance on the dataset is the k-NN algorithm. The most important features to detect cyber-attacks are basic features such as the number of seconds of a network connection, the protocol used for the connection, the network service used, normal or error status of the connection and the number of data bytes sent. The most important features to detect DoS, Probing and R2L attacks are basic features and the least important features are content features. Unlike U2R attacks, where the content features are the most important features to detect attacks.

Analysis of Pancreas Histological Images for Glucose Intolerance Identification using Wavelet Decomposition

Subtle structural differencescan be observed in the islets of Langer-hans region of microscopic image of pancreas cell of the rats having normal glucose tolerance and the rats having pre-diabetic(glucose intolerant)situa-tions. This paper proposes a way to automatically segment the islets of Langer-hans region fromthe histological image of rat's pancreas cell and on the basis of some morphological feature extracted from the segmented region the images are classified as normal and pre-diabetic.The experiment is done on a set of 134 images of which 56 are of normal type and the rests 78 are of pre-diabetictype. The work has two stages: primarily,segmentationof theregion of interest (roi)i.e. islets of Langerhansfrom the pancreatic cell and secondly, the extrac-tion of the morphological featuresfrom the region of interest for classification. Wavelet analysis and connected component analysis method have been used for automatic segmentationof the images. A few classifiers like OneRule, Naïve Bayes, MLP, J48 Tree, SVM etc.are used for evaluation among which MLP performed the best.

Extended Tree Augmented Naive Classifier

This work proposes an extended version of the well-known tree-augmented naive Bayes (TAN) classifier where the structure learning step is performed without requiring features to be connected to the class. Based on a modification of Edmonds’ algorithm, our structure learning procedure explores a superset of the structures that are considered by TAN, yet achieves global optimality of the learning score function in a very efficient way (quadratic in the number of features, the same complexity as learning TANs). A range of experiments show that we obtain models with better accuracy than TAN and comparable to the accuracy of the state-of-the-art classifier averaged one-dependence estimator.

Averaged Extended Tree Augmented Naive Classifier

This work presents a new general purpose classifier named Averaged Extended Tree Augmented Naive Bayes (AETAN), which is based on combining the advantageous characteristics of Extended Tree Augmented Naive Bayes (ETAN) and Averaged One-Dependence Estimator (AODE) classifiers. We describe the main properties of the approach and algorithms for learning it, along with an analysis of its computational time complexity. Empirical results with numerous data sets indicate that the new approach is superior to ETAN and AODE in terms of both zero-one classification accuracy and log loss. It also compares favourably against weighted AODE and hidden Naive Bayes. The learning phase of the new approach is slower than that of its competitors, while the time complexity for the testing phase is similar. Such characteristics suggest that the new classifier is ideal in scenarios where online learning is not required.

Efficient Monte Carlo optimization for multi-label classifier chains

Multi-label classification (MLC) is the supervised learning problem where an instance may be associated with multiple labels. Modeling dependencies between labels allows MLC methods to improve their performance at the expense of an increased computational cost. In this paper we focus on the classifier chains (CC) approach for modeling dependencies. On the one hand, the original CC algorithm makes a greedy approximation, and is fast but tends to propagate errors down the chain. On the other hand, a recent Bayes-optimal method improves the performance, but is computationally intractable in practice. Here we present a novel double-Monte Carlo scheme (M2CC), both for finding a good chain sequence and performing efficient inference. The M2CC algorithm remains tractable for high-dimensional data sets and obtains the best overall accuracy, as shown on several real data sets with input dimension as high as 1449 and up to 103 labels.