When the machine does not know measuring uncertainty in deep learning models of medical images

This thesis was submitted for the award of Doctor of Philosophy and was awarded by Brunel University LondonRecently, Deep learning (DL), which involves powerful black box predictors, has outperformed human experts in several medical diagnostic problems. However, these methods focus exclusively on improving the accuracy of point predictions without assessing their outputs’ quality and ignore the asymmetric cost involved in different types of misclassification errors. Neural networks also do not deliver confidence in predictions and suffer from over and under confidence, i.e. are not well calibrated. Knowing how much confidence there is in a prediction is essential for gaining clinicians’ trust in the technology. Calibrated uncertainty quantification is a challenging problem as no ground truth is available. To address this, we make two observations: (i) cost-sensitive deep neural networks with Dropweights models better quantify calibrated predictive uncertainty, and (ii) estimated uncertainty with point predictions in Deep Ensembles Bayesian Neural Networks with DropWeights can lead to a more informed decision and improve prediction quality. This dissertation focuses on quantifying uncertainty using concepts from cost-sensitive neural networks, calibration of confidence, and Dropweights ensemble method. First, we show how to improve predictive uncertainty by deep ensembles of neural networks with Dropweights learning an approximate distribution over its weights in medical image segmentation and its application in active learning. Second, we use the Jackknife resampling technique to correct bias in quantified uncertainty in image classification and propose metrics to measure uncertainty performance. The third part of the thesis is motivated by the discrepancy between the model predictive error and the objective in quantified uncertainty when costs for misclassification errors or unbalanced datasets are asymmetric. We develop cost-sensitive modifications of the neural networks in disease detection and propose metrics to measure the quality of quantified uncertainty. Finally, we leverage an adaptive binning strategy to measure uncertainty calibration error that directly corresponds to estimated uncertainty performance and address problematic evaluation methods. We evaluate the effectiveness of the tools on nuclei images segmentation, multi-class Brain MRI image classification, multi-level cell type-specific protein expression prediction in ImmunoHistoChemistry (IHC) images and cost-sensitive classification for Covid-19 detection from X-Rays and CT image dataset. Our approach is thoroughly validated by measuring the quality of uncertainty. It produces an equally good or better result and paves the way for the future that addresses the practical problems at the intersection of deep learning and Bayesian decision theory. In conclusion, our study highlights the opportunities and challenges of the application of estimated uncertainty in deep learning models of medical images, representing the confidence of the model’s prediction, and the uncertainty quality metrics show a significant improvement when using Deep Ensembles Bayesian Neural Networks with DropWeights

Machine Learning and Integrative Analysis of Biomedical Big Data.

Recent developments in high-throughput technologies have accelerated the accumulation of massive amounts of omics data from multiple sources: genome, epigenome, transcriptome, proteome, metabolome, etc. Traditionally, data from each source (e.g., genome) is analyzed in isolation using statistical and machine learning (ML) methods. Integrative analysis of multi-omics and clinical data is key to new biomedical discoveries and advancements in precision medicine. However, data integration poses new computational challenges as well as exacerbates the ones associated with single-omics studies. Specialized computational approaches are required to effectively and efficiently perform integrative analysis of biomedical data acquired from diverse modalities. In this review, we discuss state-of-the-art ML-based approaches for tackling five specific computational challenges associated with integrative analysis: curse of dimensionality, data heterogeneity, missing data, class imbalance and scalability issues

One-Class Classification: Taxonomy of Study and Review of Techniques

One-class classification (OCC) algorithms aim to build classification models when the negative class is either absent, poorly sampled or not well defined. This unique situation constrains the learning of efficient classifiers by defining class boundary just with the knowledge of positive class. The OCC problem has been considered and applied under many research themes, such as outlier/novelty detection and concept learning. In this paper we present a unified view of the general problem of OCC by presenting a taxonomy of study for OCC problems, which is based on the availability of training data, algorithms used and the application domains applied. We further delve into each of the categories of the proposed taxonomy and present a comprehensive literature review of the OCC algorithms, techniques and methodologies with a focus on their significance, limitations and applications. We conclude our paper by discussing some open research problems in the field of OCC and present our vision for future research.Comment: 24 pages + 11 pages of references, 8 figure