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Title: Knowledge extraction from biomedical data using machine learning
Authors: Lazzarini, Nicola
Issue Date: 2017
Publisher: Newcastle University
Abstract: Thanks to the breakthroughs in biotechnologies that have occurred during the recent years, biomedical data is accumulating at a previously unseen pace. In the field of biomedicine, decades-old statistical methods are still commonly used to analyse such data. However, the simplicity of these approaches often limits the amount of useful information that can be extracted from the data. Machine learning methods represent an important alternative due to their ability to capture complex patterns, within the data, likely missed by simpler methods. This thesis focuses on the extraction of useful knowledge from biomedical data using machine learning. Within the biomedical context, the vast majority of machine learning applications focus their e↵ort on the generation and validation of prediction models. Rarely the inferred models are used to discover meaningful biomedical knowledge. The work presented in this thesis goes beyond this scenario and devises new methodologies to mine machine learning models for the extraction of useful knowledge. The thesis targets two important and challenging biomedical analytic tasks: (1) the inference of biological networks and (2) the discovery of biomarkers. The first task aims to identify associations between di↵erent biological entities, while the second one tries to discover sets of variables that are relevant for specific biomedical conditions. Successful solutions for both problems rely on the ability to recognise complex interactions within the data, hence the use of multivariate machine learning methods. The network inference problem is addressed with FuNeL: a protocol to generate networks based on the analysis of rule-based machine learning models. The second task, the biomarker discovery, is studied with RGIFE, a heuristic that exploits the information extracted from machine learning models to guide its search for minimal subsets of variables. The extensive analysis conducted for this dissertation shows that the networks inferred with FuNeL capture relevant knowledge complementary to that extracted by standard inference methods. Furthermore, the associations defined by FuNeL are discovered - 6 - more pertinent in a disease context. The biomarkers selected by RGIFE are found to be disease-relevant and to have a high predictive power. When applied to osteoarthritis data, RGIFE confirmed the importance of previously identified biomarkers, whilst also extracting novel biomarkers with possible future clinical applications. Overall, the thesis shows new e↵ective methods to leverage the information, often remaining buried, encapsulated within machine learning models and discover useful biomedical knowledge.
Description: PhD Thesis
Appears in Collections:School of Computing Science

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