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.

A Comparative Analysis of Predictive Learning Algorithms on High-Dimensional Microarray Cancer Data

This research evaluates pattern recognition techniques on a subclass of big data where the dimensionality of the input space (p) is much larger than the number of observations (n). Specifically, we evaluate massive gene expression microarray cancer data where the ratio κ is less than one. We explore the statistical and computational challenges inherent in these high dimensional low sample size (HDLSS) problems and present statistical machine learning methods used to tackle and circumvent these difficulties. Regularization and kernel algorithms were explored in this research using seven datasets where κ < 1. These techniques require special attention to tuning necessitating several extensions of cross-validation to be investigated to support better predictive performance. While no single algorithm was universally the best predictor, the regularization technique produced lower test errors in five of the seven datasets studied.

Visualisation of heterogeneous data with simultaneous feature saliency using Generalised Generative Topographic Mapping

Most machine-learning algorithms are designed for datasets with features of a single type whereas very little attention has been given to datasets with mixed-type features. We recently proposed a model to handle mixed types with a probabilistic latent variable formalism. This proposed model describes the data by type-specific distributions that are conditionally independent given the latent space and is called generalised generative topographic mapping (GGTM). It has often been observed that visualisations of high-dimensional datasets can be poor in the presence of noisy features. In this paper we therefore propose to extend the GGTM to estimate feature saliency values (GGTMFS) as an integrated part of the parameter learning process with an expectation-maximisation (EM) algorithm. The efficacy of the proposed GGTMFS model is demonstrated both for synthetic and real datasets.

Inference of helicopter airframe condition

The goal of this paper is to model normal airframe conditions for helicopters in order to detect changes. This is done by inferring the flying state using a selection of sensors and frequency bands that are best for discriminating between different states. We used non-linear state-space models (NLSSM) for modelling flight conditions based on short-time frequency analysis of the vibration data and embedded the models in a switching framework to detect transitions between states. We then created a density model (using a Gaussian mixture model) for the NLSSM innovations: this provides a model for normal operation. To validate our approach, we used data with added synthetic abnormalities which was detected as low-probability periods. The model of normality gave good indications of faults during the flight, in the form of low probabilities under the model, with high accuracy (>92 %). © 2013 IEEE.

Projected sequential Gaussian processes:a C++ tool for interpolation of large datasets with heterogeneous noise

Heterogeneous datasets arise naturally in most applications due to the use of a variety of sensors and measuring platforms. Such datasets can be heterogeneous in terms of the error characteristics and sensor models. Treating such data is most naturally accomplished using a Bayesian or model-based geostatistical approach; however, such methods generally scale rather badly with the size of dataset, and require computationally expensive Monte Carlo based inference. Recently within the machine learning and spatial statistics communities many papers have explored the potential of reduced rank representations of the covariance matrix, often referred to as projected or fixed rank approaches. In such methods the covariance function of the posterior process is represented by a reduced rank approximation which is chosen such that there is minimal information loss. In this paper a sequential Bayesian framework for inference in such projected processes is presented. The observations are considered one at a time which avoids the need for high dimensional integrals typically required in a Bayesian approach. A C++ library, gptk, which is part of the INTAMAP web service, is introduced which implements projected, sequential estimation and adds several novel features. In particular the library includes the ability to use a generic observation operator, or sensor model, to permit data fusion. It is also possible to cope with a range of observation error characteristics, including non-Gaussian observation errors. Inference for the covariance parameters is explored, including the impact of the projected process approximation on likelihood profiles. We illustrate the projected sequential method in application to synthetic and real datasets. Limitations and extensions are discussed. © 2010 Elsevier Ltd.

Theological reflection at work: A phenomenological study of learning processes

Using the learning descriptions of graduates of a graduate ministry program, the mechanisms of interactions between the knowledge facets in learning processes were explored and described. The intent of the study was to explore how explicit, implicit, and emancipatory knowledge facets interacted in the learning processes at or about work. The study provided empirical research on Yang's (2003) holistic learning theory. ^ A phenomenological research design was used to explore the essence of knowledge facet interactions. I achieved epoche through the disclosure of assumptions and a written self-experience to bracket biases. A criterion based, stratified sampling strategy was used to identify participants. The sample was stratified by graduation date. The sample consisted of 11 participants and was composed primarily of married (n = 9), white, non-Hispanic (n = 10), females (n = 9), who were Roman Catholic (n = 9). Professionally, the majority of the group were teachers or professors (n = 5). ^ A semi-structured interview guide with scheduled and unscheduled probes was used. Each approximately 1-hour long interview was digitally recorded and transcribed. The transcripts were coded using a priori codes from holistic learning theory and one emergent code. The coded data were analyzed by identifying patterns, similarities, and differences under each code and then between codes. Steps to increase the trustworthiness of the study included member checks, coding checks, and thick descriptions of the data. ^ Five themes were discovered including (a) the difficulty in describing interactions between knowledge facets; (b) actual mechanisms of interactions between knowledge facets; (c) knowledge facets initiating learning and dominating learning processes; (d) the dangers of one-dimensional learning or using only one knowledge facet to learn; and (e) the role of community in learning. The interpretation confirmed, extended, and challenged holistic learning theory. Mechanisms of interaction included knowledge facets expressing, informing, changing, and guiding one another. Implications included the need for a more complex model of learning and the value of seeing spirituality in the learning process. The study raised questions for future research including exploring learning processes with people from non-Christian faith traditions or other academic disciplines and the role of spiritual identity in learning. ^

Knowledge discovery using multiple sources of biological data

The primary aim of this dissertation is to develop data mining tools for knowledge discovery in biomedical data when multiple (homogeneous or heterogeneous) sources of data are available. The central hypothesis is that, when information from multiple sources of data are used appropriately and effectively, knowledge discovery can be better achieved than what is possible from only a single source. ^ Recent advances in high-throughput technology have enabled biomedical researchers to generate large volumes of diverse types of data on a genome-wide scale. These data include DNA sequences, gene expression measurements, and much more; they provide the motivation for building analysis tools to elucidate the modular organization of the cell. The challenges include efficiently and accurately extracting information from the multiple data sources; representing the information effectively, developing analytical tools, and interpreting the results in the context of the domain. ^ The first part considers the application of feature-level integration to design classifiers that discriminate between soil types. The machine learning tools, SVM and KNN, were used to successfully distinguish between several soil samples. ^ The second part considers clustering using multiple heterogeneous data sources. The resulting Multi-Source Clustering (MSC) algorithm was shown to have a better performance than clustering methods that use only a single data source or a simple feature-level integration of heterogeneous data sources. ^ The third part proposes a new approach to effectively incorporate incomplete data into clustering analysis. Adapted from K-means algorithm, the Generalized Constrained Clustering (GCC) algorithm makes use of incomplete data in the form of constraints to perform exploratory analysis. Novel approaches for extracting constraints were proposed. For sufficiently large constraint sets, the GCC algorithm outperformed the MSC algorithm. ^ The last part considers the problem of providing a theme-specific environment for mining multi-source biomedical data. The database called PlasmoTFBM, focusing on gene regulation of Plasmodium falciparum, contains diverse information and has a simple interface to allow biologists to explore the data. It provided a framework for comparing different analytical tools for predicting regulatory elements and for designing useful data mining tools. ^ The conclusion is that the experiments reported in this dissertation strongly support the central hypothesis.^

Two -way direction of influence in mother-infant interaction as denoted by concurrent reciprocal learning processes

This series of 5 single-subject studies used the operant conditioning paradigm to investigate, within the two-way influence process, how (a) contingent infant attention can reinforce maternal verbal behaviors during a period of mother-infant interaction and under subsequent experimental manipulation. Differential reinforcement was used to determine if it is possible that an infant attending to the mother (denoted by head-turns towards the image of the mother plus eye contact) increases (reinforces) the mother's verbal response (to a cue from the infant) upon which the infant behavior is contingent. There was also (b) an evaluation during the contrived parent-infant interaction for concurrent operant learning of infant vocal behavior via contingent verbal responding (reinforcement) implemented by the mother. Further, it was noted (c) whether or not the mother reported being aware that her responses were influenced by the infant's behavior. Findings showed: the operant conditioning of the maternal verbal behaviors were reinforced by contingent infant attention; and the operant conditioning of infant vocalizations was reinforced by contingent maternal verbal behaviors. No parent reported (1) being aware of the increase in their verbal response reinforced during operant conditioning of parental behavior nor a decrease in those responses during the DRA reversal phase, or (2) noticing a contingency between infant's and mother's response. By binomial 1-tail tests, the verbal-behavior patterns of the 5 mothers were conditioned by infant reinforcement (p < 0.02) and, concurrently, the vocal-response patterns of the 5 infants were conditioned by maternal reinforcement (p < 0.02). A program of systematic empirical research on the determinants of concurrent conditioning within mother-child interaction may provide a way to evaluate the differential effectiveness of interventions aimed at improving parent-child interactions. The work conducted in the present study is one step in this direction. ^

XML storage and retrieval using the semantic binary object -oriented database system (SEM-ODB)

Over the past five years, XML has been embraced by both the research and industrial community due to its promising prospects as a new data representation and exchange format on the Internet. The widespread popularity of XML creates an increasing need to store XML data in persistent storage systems and to enable sophisticated XML queries over the data. The currently available approaches to addressing the XML storage and retrieval issue have the limitations of either being not mature enough (e.g. native approaches) or causing inflexibility, a lot of fragmentation and excessive join operations (e.g. non-native approaches such as the relational database approach). ^ In this dissertation, I studied the issue of storing and retrieving XML data using the Semantic Binary Object-Oriented Database System (Sem-ODB) to leverage the advanced Sem-ODB technology with the emerging XML data model. First, a meta-schema based approach was implemented to address the data model mismatch issue that is inherent in the non-native approaches. The meta-schema based approach captures the meta-data of both Document Type Definitions (DTDs) and Sem-ODB Semantic Schemas, thus enables a dynamic and flexible mapping scheme. Second, a formal framework was presented to ensure precise and concise mappings. In this framework, both schemas and the conversions between them are formally defined and described. Third, after major features of an XML query language, XQuery, were analyzed, a high-level XQuery to Semantic SQL (Sem-SQL) query translation scheme was described. This translation scheme takes advantage of the navigation-oriented query paradigm of the Sem-SQL, thus avoids the excessive join problem of relational approaches. Finally, the modeling capability of the Semantic Binary Object-Oriented Data Model (Sem-ODM) was explored from the perspective of conceptually modeling an XML Schema using a Semantic Schema. ^ It was revealed that the advanced features of the Sem-ODB, such as multi-valued attributes, surrogates, the navigation-oriented query paradigm, among others, are indeed beneficial in coping with the XML storage and retrieval issue using a non-XML approach. Furthermore, extensions to the Sem-ODB to make it work more effectively with XML data were also proposed. ^

Sistema inteligente para o processamento de imagens digitais intrabucais oclusais

Several are the areas in which digital images are used in solving day-to-day problems. In medicine the use of computer systems have improved the diagnosis and medical interpretations. In dentistry it’s not different, increasingly procedures assisted by computers have support dentists in their tasks. Set in this context, an area of dentistry known as public oral health is responsible for diagnosis and oral health treatment of a population. To this end, oral visual inspections are held in order to obtain oral health status information of a given population. From this collection of information, also known as epidemiological survey, the dentist can plan and evaluate taken actions for the different problems identified. This procedure has limiting factors, such as a limited number of qualified professionals to perform these tasks, different diagnoses interpretations among other factors. Given this context came the ideia of using intelligent systems techniques in supporting carrying out these tasks. Thus, it was proposed in this paper the development of an intelligent system able to segment, count and classify teeth from occlusal intraoral digital photographic images. The proposed system makes combined use of machine learning techniques and digital image processing. We first carried out a color-based segmentation on regions of interest, teeth and non teeth, in the images through the use of Support Vector Machine. After identifying these regions were used techniques based on morphological operators such as erosion and transformed watershed for counting and detecting the boundaries of the teeth, respectively. With the border detection of teeth was possible to calculate the Fourier descriptors for their shape and the position descriptors. Then the teeth were classified according to their types through the use of the SVM from the method one-against-all used in multiclass problem. The multiclass classification problem has been approached in two different ways. In the first approach we have considered three class types: molar, premolar and non teeth, while the second approach were considered five class types: molar, premolar, canine, incisor and non teeth. The system presented a satisfactory performance in the segmenting, counting and classification of teeth present in the images.

Sistema inteligente para o processamento de imagens digitais intrabucais oclusais

Several are the areas in which digital images are used in solving day-to-day problems. In medicine the use of computer systems have improved the diagnosis and medical interpretations. In dentistry it’s not different, increasingly procedures assisted by computers have support dentists in their tasks. Set in this context, an area of dentistry known as public oral health is responsible for diagnosis and oral health treatment of a population. To this end, oral visual inspections are held in order to obtain oral health status information of a given population. From this collection of information, also known as epidemiological survey, the dentist can plan and evaluate taken actions for the different problems identified. This procedure has limiting factors, such as a limited number of qualified professionals to perform these tasks, different diagnoses interpretations among other factors. Given this context came the ideia of using intelligent systems techniques in supporting carrying out these tasks. Thus, it was proposed in this paper the development of an intelligent system able to segment, count and classify teeth from occlusal intraoral digital photographic images. The proposed system makes combined use of machine learning techniques and digital image processing. We first carried out a color-based segmentation on regions of interest, teeth and non teeth, in the images through the use of Support Vector Machine. After identifying these regions were used techniques based on morphological operators such as erosion and transformed watershed for counting and detecting the boundaries of the teeth, respectively. With the border detection of teeth was possible to calculate the Fourier descriptors for their shape and the position descriptors. Then the teeth were classified according to their types through the use of the SVM from the method one-against-all used in multiclass problem. The multiclass classification problem has been approached in two different ways. In the first approach we have considered three class types: molar, premolar and non teeth, while the second approach were considered five class types: molar, premolar, canine, incisor and non teeth. The system presented a satisfactory performance in the segmenting, counting and classification of teeth present in the images.

Mapped cetacean habitat suitability and richness in the Azores, links to ArcGIS files

Marine spatial planning and ecological research call for high-resolution species distribution data. However, those data are still not available for most marine large vertebrates. The dynamic nature of oceanographic processes and the wide-ranging behavior of many marine vertebrates create further difficulties, as distribution data must incorporate both the spatial and temporal dimensions. Cetaceans play an essential role in structuring and maintaining marine ecosystems and face increasing threats from human activities. The Azores holds a high diversity of cetaceans but the information about spatial and temporal patterns of distribution for this marine megafauna group in the region is still very limited. To tackle this issue, we created monthly predictive cetacean distribution maps for spring and summer months, using data collected by the Azores Fisheries Observer Programme between 2004 and 2009. We then combined the individual predictive maps to obtain species richness maps for the same period. Our results reflect a great heterogeneity in distribution among species and within species among different months. This heterogeneity reflects a contrasting influence of oceanographic processes on the distribution of cetacean species. However, some persistent areas of increased species richness could also be identified from our results. We argue that policies aimed at effectively protecting cetaceans and their habitats must include the principle of dynamic ocean management coupled with other area-based management such as marine spatial planning.

Probing Tissue Microstructure Using Susceptibility Contrast Magnetic Resonance Imaging

Magnetic resonance imaging is a research and clinical tool that has been applied in a wide variety of sciences. One area of magnetic resonance imaging that has exhibited terrific promise and growth in the past decade is magnetic susceptibility imaging. Imaging tissue susceptibility provides insight into the microstructural organization and chemical properties of biological tissues, but this image contrast is not well understood. The purpose of this work is to develop effective approaches to image, assess, and model the mechanisms that generate both isotropic and anisotropic magnetic susceptibility contrast in biological tissues, including myocardium and central nervous system white matter.

This document contains the first report of MRI-measured susceptibility anisotropy in myocardium. Intact mouse heart specimens were scanned using MRI at 9.4 T to ascertain both the magnetic susceptibility and myofiber orientation of the tissue. The susceptibility anisotropy of myocardium was observed and measured by relating the apparent tissue susceptibility as a function of the myofiber angle with respect to the applied magnetic field. A multi-filament model of myocardial tissue revealed that the diamagnetically anisotropy α-helix peptide bonds in myofilament proteins are capable of producing bulk susceptibility anisotropy on a scale measurable by MRI, and are potentially the chief sources of the experimentally observed anisotropy.

The growing use of paramagnetic contrast agents in magnetic susceptibility imaging motivated a series of investigations regarding the effect of these exogenous agents on susceptibility imaging in the brain, heart, and kidney. In each of these organs, gadolinium increases susceptibility contrast and anisotropy, though the enhancements depend on the tissue type, compartmentalization of contrast agent, and complex multi-pool relaxation. In the brain, the introduction of paramagnetic contrast agents actually makes white matter tissue regions appear more diamagnetic relative to the reference susceptibility. Gadolinium-enhanced MRI yields tensor-valued susceptibility images with eigenvectors that more accurately reflect the underlying tissue orientation.

Despite the boost gadolinium provides, tensor-valued susceptibility image reconstruction is prone to image artifacts. A novel algorithm was developed to mitigate these artifacts by incorporating orientation-dependent tissue relaxation information into susceptibility tensor estimation. The technique was verified using a numerical phantom simulation, and improves susceptibility-based tractography in the brain, kidney, and heart. This work represents the first successful application of susceptibility-based tractography to a whole, intact heart.

The knowledge and tools developed throughout the course of this research were then applied to studying mouse models of Alzheimer’s disease in vivo, and studying hypertrophic human myocardium specimens ex vivo. Though a preliminary study using contrast-enhanced quantitative susceptibility mapping has revealed diamagnetic amyloid plaques associated with Alzheimer’s disease in the mouse brain ex vivo, non-contrast susceptibility imaging was unable to precisely identify these plaques in vivo. Susceptibility tensor imaging of human myocardium specimens at 9.4 T shows that susceptibility anisotropy is larger and mean susceptibility is more diamagnetic in hypertrophic tissue than in normal tissue. These findings support the hypothesis that myofilament proteins are a source of susceptibility contrast and anisotropy in myocardium. This collection of preclinical studies provides new tools and context for analyzing tissue structure, chemistry, and health in a variety of organs throughout the body.

Learning from Geometry

Subspaces and manifolds are two powerful models for high dimensional signals. Subspaces model linear correlation and are a good fit to signals generated by physical systems, such as frontal images of human faces and multiple sources impinging at an antenna array. Manifolds model sources that are not linearly correlated, but where signals are determined by a small number of parameters. Examples are images of human faces under different poses or expressions, and handwritten digits with varying styles. However, there will always be some degree of model mismatch between the subspace or manifold model and the true statistics of the source. This dissertation exploits subspace and manifold models as prior information in various signal processing and machine learning tasks.

A near-low-rank Gaussian mixture model measures proximity to a union of linear or affine subspaces. This simple model can effectively capture the signal distribution when each class is near a subspace. This dissertation studies how the pairwise geometry between these subspaces affects classification performance. When model mismatch is vanishingly small, the probability of misclassification is determined by the product of the sines of the principal angles between subspaces. When the model mismatch is more significant, the probability of misclassification is determined by the sum of the squares of the sines of the principal angles. Reliability of classification is derived in terms of the distribution of signal energy across principal vectors. Larger principal angles lead to smaller classification error, motivating a linear transform that optimizes principal angles. This linear transformation, termed TRAIT, also preserves some specific features in each class, being complementary to a recently developed Low Rank Transform (LRT). Moreover, when the model mismatch is more significant, TRAIT shows superior performance compared to LRT.

The manifold model enforces a constraint on the freedom of data variation. Learning features that are robust to data variation is very important, especially when the size of the training set is small. A learning machine with large numbers of parameters, e.g., deep neural network, can well describe a very complicated data distribution. However, it is also more likely to be sensitive to small perturbations of the data, and to suffer from suffer from degraded performance when generalizing to unseen (test) data.

From the perspective of complexity of function classes, such a learning machine has a huge capacity (complexity), which tends to overfit. The manifold model provides us with a way of regularizing the learning machine, so as to reduce the generalization error, therefore mitigate overfiting. Two different overfiting-preventing approaches are proposed, one from the perspective of data variation, the other from capacity/complexity control. In the first approach, the learning machine is encouraged to make decisions that vary smoothly for data points in local neighborhoods on the manifold. In the second approach, a graph adjacency matrix is derived for the manifold, and the learned features are encouraged to be aligned with the principal components of this adjacency matrix. Experimental results on benchmark datasets are demonstrated, showing an obvious advantage of the proposed approaches when the training set is small.

Stochastic optimization makes it possible to track a slowly varying subspace underlying streaming data. By approximating local neighborhoods using affine subspaces, a slowly varying manifold can be efficiently tracked as well, even with corrupted and noisy data. The more the local neighborhoods, the better the approximation, but the higher the computational complexity. A multiscale approximation scheme is proposed, where the local approximating subspaces are organized in a tree structure. Splitting and merging of the tree nodes then allows efficient control of the number of neighbourhoods. Deviation (of each datum) from the learned model is estimated, yielding a series of statistics for anomaly detection. This framework extends the classical {\em changepoint detection} technique, which only works for one dimensional signals. Simulations and experiments highlight the robustness and efficacy of the proposed approach in detecting an abrupt change in an otherwise slowly varying low-dimensional manifold.

Occupant location prediction in smart buildings using association rule mining

Heating, ventilation, air conditioning (HVAC) systems are significant consumers of energy, however building management systems do not typically operate them in accordance with occupant movements. Due to the delayed response of HVAC systems, prediction of occupant locations is necessary to maximize energy efficiency. We present an approach to occupant location prediction based on association rule mining, allowing prediction based on historical occupant locations. Association rule mining is a machine learning technique designed to find any correlations which exist in a given dataset. Occupant location datasets have a number of properties which differentiate them from the market basket datasets that association rule mining was originally designed for. This thesis adapts the approach to suit such datasets, focusing the rule mining process on patterns which are useful for location prediction. This approach, named OccApriori, allows for the prediction of occupants’ next locations as well as their locations further in the future, and can take into account any available data, for example the day of the week, the recent movements of the occupant, and timetable data. By integrating an existing extension of association rule mining into the approach, it is able to make predictions based on general classes of locations as well as specific locations.