Mass spectral imaging of clinical samples using deep learning

A better interpretation of tumour heterogeneity and variability is vital for the improvement of novel diagnostic techniques and personalized cancer treatments. Tumour tissue heterogeneity is characterized by biochemical heterogeneity, which can be investigated by unsupervised metabolomics. Mass Spectrometry Imaging (MSI) combined with Machine Learning techniques have generated increasing interest as analytical and diagnostic tools for the analysis of spatial molecular patterns in tissue samples. Considering the high complexity of data produced by the application of MSI, which can consist of many thousands of spectral peaks, statistical analysis and in particular machine learning and deep learning have been investigated as novel approaches to deduce the relationships between the measured molecular patterns and the local structural and biological properties of the tissues. Machine learning have historically been divided into two main categories: Supervised and Unsupervised learning. In MSI, supervised learning methods may be used to segment tissues into histologically relevant areas e.g. the classification of tissue regions in H&E (Haemotoxylin and Eosin) stained samples. Initial classification by an expert histopathologist, through visual inspection enables the development of univariate or multivariate models, based on tissue regions that have significantly up/down-regulated ions. However, complex data may result in underdetermined models, and alternative methods that can cope with high dimensionality and noisy data are required. Here, we describe, apply, and test a novel diagnostic procedure built using a combination of MSI and deep learning with the objective of delineating and identifying biochemical differences between cancerous and non-cancerous tissue in metastatic liver cancer and epithelial ovarian cancer. The workflow investigates the robustness of single (1D) to multidimensional (3D) tumour analyses and also highlights possible biomarkers which are not accessible from classical visual analysis of the H&E images. The identification of key molecular markers may provide a deeper understanding of tumour heterogeneity and potential targets for intervention.Open Acces

Quantitative electron microscopy for microstructural characterisation

Development of materials for high-performance applications requires accurate and useful analysis tools. In parallel with advances in electron microscopy hardware, we require analysis approaches to better understand microstructural behaviour. Such improvements in characterisation capability permit informed alloy design. New approaches to the characterisation of metallic materials are presented, primarily using signals collected from electron microscopy experiments. Electron backscatter diffraction is regularly used to investigate crystallography in the scanning electron microscope, and combined with energy-dispersive X-ray spectroscopy to simultaneusly investigate chemistry. New algorithms and analysis pipelines are developed to permit accurate and routine microstructural evaluation, leveraging a variety of machine learning approaches. This thesis investigates the structure and behaviour of Co/Ni-base superalloys, derived from V208C. Use of the presently developed techniques permits informed development of a new generation of advanced gas turbine engine materials.Open Acces

Temporally adaptive monitoring procedures with applications in enterprise cyber-security

Due to the perpetual threat of cyber-attacks, enterprises must employ and develop new methods of detection as attack vectors evolve and advance. Enterprise computer networks produce a large volume and variety of data including univariate data streams, time series and network graph streams. Motivated by cyber-security, this thesis develops adaptive monitoring tools for univariate and network graph data streams, however, they are not limited to this domain. In all domains, real data streams present several challenges for monitoring including trend, periodicity and change points. Streams often also have high volume and frequency. To deal with the non-stationarity in the data, the methods applied must be adaptive. Adaptability in the proposed procedures throughout the thesis is introduced using forgetting factors, weighting the data accordingly to recency. Secondly, methods applied must be computationally fast with a small or fixed computation burden and fixed storage requirements for timely processing. Throughout this thesis, sequential or sliding window approaches are employed to achieve this. The first part of the thesis is centred around univariate monitoring procedures. A sequential adaptive parameter estimator is proposed using a Bayesian framework. This procedure is then extended for multiple change point detection, where, unlike existing change point procedures, the proposed method is capable of detecting abrupt changes in the presence of trend. We additionally present a time series model which combines short-term and long-term behaviours of a series for improved anomaly detection. Unlike existing methods which primarily focus on point anomalies detection (extreme outliers), our method is capable of also detecting contextual anomalies, when the data deviates from persistent patterns of the series such as seasonality. Finally, a novel multi-type relational clustering methodology is proposed. As multiple relations exist between the different entities within a network (computers, users and ports), multiple network graphs can be generated. We propose simultaneously clustering over all graphs to produce a single clustering for each entity using Non-Negative Matrix Tri-Factorisation. Through simplifications, the proposed procedure is fast and scalable for large network graphs. Additionally, this methodology is extended for graph streams. This thesis provides an assortment of tools for enterprise network monitoring with a focus on adaptability and scalability making them suitable for intrusion detection and situational awareness.Open Acces

An Unsupervised Approach to Modelling Visual Data

For very large visual datasets, producing expert ground-truth data for training supervised algorithms can represent a substantial human effort. In these situations there is scope for the use of unsupervised approaches that can model collections of images and automatically summarise their content. The primary motivation for this thesis comes from the problem of labelling large visual datasets of the seafloor obtained by an Autonomous Underwater Vehicle (AUV) for ecological analysis. It is expensive to label this data, as taxonomical experts for the specific region are required, whereas automatically generated summaries can be used to focus the efforts of experts, and inform decisions on additional sampling. The contributions in this thesis arise from modelling this visual data in entirely unsupervised ways to obtain comprehensive visual summaries. Firstly, popular unsupervised image feature learning approaches are adapted to work with large datasets and unsupervised clustering algorithms. Next, using Bayesian models the performance of rudimentary scene clustering is boosted by sharing clusters between multiple related datasets, such as regular photo albums or AUV surveys. These Bayesian scene clustering models are extended to simultaneously cluster sub-image segments to form unsupervised notions of “objects” within scenes. The frequency distribution of these objects within scenes is used as the scene descriptor for simultaneous scene clustering. Finally, this simultaneous clustering model is extended to make use of whole image descriptors, which encode rudimentary spatial information, as well as object frequency distributions to describe scenes. This is achieved by unifying the previously presented Bayesian clustering models, and in so doing rectifies some of their weaknesses and limitations. Hence, the final contribution of this thesis is a practical unsupervised algorithm for modelling images from the super-pixel to album levels, and is applicable to large datasets

Speech Recognition

Chapters in the first part of the book cover all the essential speech processing techniques for building robust, automatic speech recognition systems: the representation for speech signals and the methods for speech-features extraction, acoustic and language modeling, efficient algorithms for searching the hypothesis space, and multimodal approaches to speech recognition. The last part of the book is devoted to other speech processing applications that can use the information from automatic speech recognition for speaker identification and tracking, for prosody modeling in emotion-detection systems and in other speech processing applications that are able to operate in real-world environments, like mobile communication services and smart homes