Automatic quantification of brain midline shift in CT images

Ph.DDOCTOR OF PHILOSOPH

Sparse machine learning models in bioinformatics

The meaning of parsimony is twofold in machine learning: either the structure or (and) the parameter of a model can be sparse. Sparse models have many strengths. First, sparsity is an important regularization principle to reduce model complexity and therefore avoid overfitting. Second, in many fields, for example bioinformatics, many high-dimensional data may be generated by a very few number of hidden factors, thus it is more reasonable to use a proper sparse model than a dense model. Third, a sparse model is often easy to interpret. In this dissertation, we investigate the sparse machine learning models and their applications in high-dimensional biological data analysis. We focus our research on five types of sparse models as follows. First, sparse representation is a parsimonious principle that a sample can be approximated by a sparse linear combination of basis vectors. We explore existing sparse representation models and propose our own sparse representation methods for high dimensional biological data analysis. We derive different sparse representation models from a Bayesian perspective. Two generic dictionary learning frameworks are proposed. Also, kernel and supervised dictionary learning approaches are devised. Furthermore, we propose fast active-set and decomposition methods for the optimization of sparse coding models. Second, gene-sample-time data are promising in clinical study, but challenging in computation. We propose sparse tensor decomposition methods and kernel methods for the dimensionality reduction and classification of such data. As the extensions of matrix factorization, tensor decomposition techniques can reduce the dimensionality of the gene-sample-time data dramatically, and the kernel methods can run very efficiently on such data. Third, we explore two sparse regularized linear models for multi-class problems in bioinformatics. Our first method is called the nearest-border classification technique for data with many classes. Our second method is a hierarchical model. It can simultaneously select features and classify samples. Our experiment, on breast tumor subtyping, shows that this model outperforms the one-versus-all strategy in some cases. Fourth, we propose to use spectral clustering approaches for clustering microarray time-series data. The approaches are based on two transformations that have been recently introduced, especially for gene expression time-series data, namely, alignment-based and variation-based transformations. Both transformations have been devised in order to take into account temporal relationships in the data, and have been shown to increase the ability of a clustering method in detecting co-expressed genes. We investigate the performances of these transformations methods, when combined with spectral clustering on two microarray time-series datasets, and discuss their strengths and weaknesses. Our experiments on two well known real-life datasets show the superiority of the alignment-based over the variation-based transformation for finding meaningful groups of co-expressed genes. Fifth, we propose the max-min high-order dynamic Bayesian network (MMHO-DBN) learning algorithm, in order to reconstruct time-delayed gene regulatory networks. Due to the small sample size of the training data and the power-low nature of gene regulatory networks, the structure of the network is restricted by sparsity. We also apply the qualitative probabilistic networks (QPNs) to interpret the interactions learned. Our experiments on both synthetic and real gene expression time-series data show that, MMHO-DBN can obtain better precision than some existing methods, and perform very fast. The QPN analysis can accurately predict types of influences and synergies. Additionally, since many high dimensional biological data are subject to missing values, we survey various strategies for learning models from incomplete data. We extend the existing imputation methods, originally for two-way data, to methods for gene-sample-time data. We also propose a pair-wise weighting method for computing kernel matrices from incomplete data. Computational evaluations show that both approaches work very robustly

Two-Level Text Classification Using Hybrid Machine Learning Techniques

Nowadays, documents are increasingly being associated with multi-level category hierarchies rather than a flat category scheme. To access these documents in real time, we need fast automatic methods to navigate these hierarchies. Today’s vast data repositories such as the web also contain many broad domains of data which are quite distinct from each other e.g. medicine, education, sports and politics. Each domain constitutes a subspace of the data within which the documents are similar to each other but quite distinct from the documents in another subspace. The data within these domains is frequently further divided into many subcategories. Subspace Learning is a technique popular with non-text domains such as image recognition to increase speed and accuracy. Subspace analysis lends itself naturally to the idea of hybrid classifiers. Each subspace can be processed by a classifier best suited to the characteristics of that particular subspace. Instead of using the complete set of full space feature dimensions, classifier performances can be boosted by using only a subset of the dimensions. This thesis presents a novel hybrid parallel architecture using separate classifiers trained on separate subspaces to improve two-level text classification. The classifier to be used on a particular input and the relevant feature subset to be extracted is determined dynamically by using a novel method based on the maximum significance value. A novel vector representation which enhances the distinction between classes within the subspace is also developed. This novel system, the Hybrid Parallel Classifier, was compared against the baselines of several single classifiers such as the Multilayer Perceptron and was found to be faster and have higher two-level classification accuracies. The improvement in performance achieved was even higher when dealing with more complex category hierarchies

Two-level text classification using hybrid machine learning techniques

Nowadays, documents are increasingly being associated with multi-level category hierarchies rather than a flat category scheme. To access these documents in real time, we need fast automatic methods to navigate these hierarchies. Today’s vast data repositories such as the web also contain many broad domains of data which are quite distinct from each other e.g. medicine, education, sports and politics. Each domain constitutes a subspace of the data within which the documents are similar to each other but quite distinct from the documents in another subspace. The data within these domains is frequently further divided into many subcategories. Subspace Learning is a technique popular with non-text domains such as image recognition to increase speed and accuracy. Subspace analysis lends itself naturally to the idea of hybrid classifiers. Each subspace can be processed by a classifier best suited to the characteristics of that particular subspace. Instead of using the complete set of full space feature dimensions, classifier performances can be boosted by using only a subset of the dimensions. This thesis presents a novel hybrid parallel architecture using separate classifiers trained on separate subspaces to improve two-level text classification. The classifier to be used on a particular input and the relevant feature subset to be extracted is determined dynamically by using a novel method based on the maximum significance value. A novel vector representation which enhances the distinction between classes within the subspace is also developed. This novel system, the Hybrid Parallel Classifier, was compared against the baselines of several single classifiers such as the Multilayer Perceptron and was found to be faster and have higher two-level classification accuracies. The improvement in performance achieved was even higher when dealing with more complex category hierarchies.EThOS - Electronic Theses Online ServiceGBUnited Kingdo

Personalised antimicrobial management in secondary care

Background: The growing threat of Antimicrobial Resistance (AMR) requires innovative methods to promote the sustainable effectiveness of antimicrobial agents. Hypothesis: This thesis aimed to explore the hypothesis that personalised decision support interventions have the utility to enhance antimicrobial management across secondary care. Methods: Different research methods were used to investigate this hypothesis. Individual physician decision making was mapped and patient experiences of engagement with decision making explored using semi-structured interviews. Cross-specialty engagement with antimicrobial management was investigated through cross-sectional analysis of conference abstracts and educational training curricula. Artificial intelligence tools were developed to explore their ability to predict the likelihood of infection and provide individualised prescribing recommendations using routine patient data. Dynamic, individualised dose optimisation was explored through: (i) development of a microneedle based, electrochemical biosensor for minimally invasive monitoring of beta-lactams; and (ii) pharmacokinetic (PK)-pharmacodynamic (PD) modelling of a new PK-PD index using C-Reactive protein (CRP) to predict the pharmacodynamics of vancomycin. Ethics approval was granted for all aspects of work explored within this thesis. Results: Mapping of individual physician decision making during infection management demonstrated several areas where personalised, technological interventions could enhance antimicrobial management. At specialty level, non-infection specialties have little engagement with antimicrobial management. The importance of engaging surgical specialties, who have relatively high rates of antimicrobial usage and healthcare associated infections, was observed. An individualised information leaflet, co-designed with patients, to provide personalised infection information to in-patients receiving antibiotics significantly improved knowledge and reported engagement with decision making. Artificial intelligence was able to enhance the prediction of infection and the prescribing of antimicrobials using routinely available clinical data. Real-time, continuous penicillin monitoring was demonstrated using a microneedle based electrochemical sensor in-vivo. A new PK-PD index, using C-Reactive Protein, was able to predict individual patient response to vancomycin therapy at 96-120 hours of therapy. Conclusion: Through co-design and the application of specific technologies it is possible to provide personalised antimicrobial management within secondary care.Open Acces