Compressing medical images with minimal information loss

This thesis aims to explore the potentialities of neural networks as compression algorithms for medical images. The objective is to develop a compressed image representation suitable for image comparison. In particular we studied different autoencoder architectures, varying the encoding mechanism in order to achieve a high degree of compression while also retaining a meaningful feature space. Our work is focused on mammograms but the methods introduced here can be extrapolated to other types of medical images

Data-analysis strategies for image-based cell profiling

Image-based cell profiling is a high-throughput strategy for the quantification of phenotypic differences among a variety of cell populations. It paves the way to studying biological systems on a large scale by using chemical and genetic perturbations. The general workflow for this technology involves image acquisition with high-throughput microscopy systems and subsequent image processing and analysis. Here, we introduce the steps required to create high-quality image-based (i.e., morphological) profiles from a collection of microscopy images. We recommend techniques that have proven useful in each stage of the data analysis process, on the basis of the experience of 20 laboratories worldwide that are refining their image-based cell-profiling methodologies in pursuit of biological discovery. The recommended techniques cover alternatives that may suit various biological goals, experimental designs, and laboratories' preferences.Peer reviewe

Computing Interpretable Representations of Cell Morphodynamics

Shape changes (morphodynamics) are one of the principal ways cells interact with their environments and perform key intrinsic behaviours like division. These dynamics arise from a myriad of complex signalling pathways that often organise with emergent simplicity to carry out critical functions including predation, collaboration and migration. A powerful method for analysis can therefore be to quantify this emergent structure, bypassing the low-level complexity. Enormous image datasets are now available to mine. However, it can be difficult to uncover interpretable representations of the global organisation of these heterogeneous dynamic processes. Here, such representations were developed for interpreting morphodynamics in two key areas: mode of action (MoA) comparison for drug discovery (developed using the economically devastating Asian soybean rust crop pathogen) and 3D migration of immune system T cells through extracellular matrices (ECMs). For MoA comparison, population development over a 2D space of shapes (morphospace) was described using two models with condition-dependent parameters: a top-down model of diffusive development over Waddington-type landscapes, and a bottom-up model of tip growth. A variety of landscapes were discovered, describing phenotype transitions during growth, and possible perturbations in the tip growth machinery that cause this variation were identified. For interpreting T cell migration, a new 3D shape descriptor that incorporates key polarisation information was developed, revealing low-dimensionality of shape, and the distinct morphodynamics of run-and-stop modes that emerge at minute timescales were mapped. Periodically oscillating morphodynamics that include retrograde deformation flows were found to underlie active translocation (run mode). Overall, it was found that highly interpretable representations could be uncovered while still leveraging the enormous discovery power of deep learning algorithms. The results show that whole-cell morphodynamics can be a convenient and powerful place to search for structure, with potentially life-saving applications in medicine and biocide discovery as well as immunotherapeutics.Open Acces

Machine Learning Methods To Identify Hidden Phenotypes In The Electronic Health Record

The widespread adoption of Electronic Health Records (EHRs) means an unprecedented amount of patient treatment and outcome data is available to researchers. Research is a tertiary priority in the EHR, where the priorities are patient care and billing. Because of this, the data is not standardized or formatted in a manner easily adapted to machine learning approaches. Data may be missing for a large variety of reasons ranging from individual input styles to differences in clinical decision making, for example, which lab tests to issue. Few patients are annotated at a research quality, limiting sample size and presenting a moving gold standard. Patient progression over time is key to understanding many diseases but many machine learning algorithms require a snapshot, at a single time point, to create a usable vector form. In this dissertation, we develop new machine learning methods and computational workflows to extract hidden phenotypes from the Electronic Health Record (EHR). In Part 1, we use a semi-supervised deep learning approach to compensate for the low number of research quality labels present in the EHR. In Part 2, we examine and provide recommendations for characterizing and managing the large amount of missing data inherent to EHR data. In Part 3, we present an adversarial approach to generate synthetic data that closely resembles the original data while protecting subject privacy. We also introduce a workflow to enable reproducible research even when data cannot be shared. In Part 4, we introduce a novel strategy to first extract sequential data from the EHR and then demonstrate the ability to model these sequences with deep learning