Handling of uncertainty in medical data using machine learning and probability theory techniques: a review of 30 years (1991-2020).

Understanding the data and reaching accurate conclusions are of paramount importance in the present era of big data. Machine learning and probability theory methods have been widely used for this purpose in various fields. One critically important yet less explored aspect is capturing and analyzing uncertainties in the data and model. Proper quantification of uncertainty helps to provide valuable information to obtain accurate diagnosis. This paper reviewed related studies conducted in the last 30 years (from 1991 to 2020) in handling uncertainties in medical data using probability theory and machine learning techniques. Medical data is more prone to uncertainty due to the presence of noise in the data. So, it is very important to have clean medical data without any noise to get accurate diagnosis. The sources of noise in the medical data need to be known to address this issue. Based on the medical data obtained by the physician, diagnosis of disease, and treatment plan are prescribed. Hence, the uncertainty is growing in healthcare and there is limited knowledge to address these problems. Our findings indicate that there are few challenges to be addressed in handling the uncertainty in medical raw data and new models. In this work, we have summarized various methods employed to overcome this problem. Nowadays, various novel deep learning techniques have been proposed to deal with such uncertainties and improve the performance in decision making.

DeepTRIAGE: interpretable and individualised biomarker scores using attention mechanism for the classification of breast cancer sub-types.

BACKGROUND: Breast cancer is a collection of multiple tissue pathologies, each with a distinct molecular signature that correlates with patient prognosis and response to therapy. Accurately differentiating between breast cancer sub-types is an important part of clinical decision-making. Although this problem has been addressed using machine learning methods in the past, there remains unexplained heterogeneity within the established sub-types that cannot be resolved by the commonly used classification algorithms. METHODS: In this paper, we propose a novel deep learning architecture, called DeepTRIAGE (Deep learning for the TRactable Individualised Analysis of Gene Expression), which uses an attention mechanism to obtain personalised biomarker scores that describe how important each gene is in predicting the cancer sub-type for each sample. We then perform a principal component analysis of these biomarker scores to visualise the sample heterogeneity, and use a linear model to test whether the major principal axes associate with known clinical phenotypes. RESULTS: Our model not only classifies cancer sub-types with good accuracy, but simultaneously assigns each patient their own set of interpretable and individualised biomarker scores. These personalised scores describe how important each feature is in the classification of any patient, and can be analysed post-hoc to generate new hypotheses about latent heterogeneity. CONCLUSIONS: We apply the DeepTRIAGE framework to classify the gene expression signatures of luminal A and luminal B breast cancer sub-types, and illustrate its use for genes as well as the GO and KEGG gene sets. Using DeepTRIAGE, we calculate personalised biomarker scores that describe the most important features for classifying an individual patient as luminal A or luminal B. In doing so, DeepTRIAGE simultaneously reveals heterogeneity within the luminal A biomarker scores that significantly associate with tumour stage, placing all luminal samples along a continuum of severity.