Is eXplainable AI suitable as a hypotheses generating tool for medical research? Comparing basic pathology annotation with heat maps to find out

Abstract: Hypothesis testing has long been a formal and standardized process. Hypothesis generation, on the other hand, remains largely informal. This thesis assess whether eXplainable AI (XAI) can aid in the standardization of hypothesis generation through its utilization as a hypothesis generating tool for medical research. We produce XAI heat maps for a Convolutional Neural Network (CNN) trained to classify Microsatellite Instability (MSI) in colon and gastric cancer with four different XAI methods: Guided Backpropagation, VarGrad, Grad-CAM and Sobol Attribution. We then compare these heat maps with pathology annotations in order to look for differences to turn into new hypotheses. Our CNN successfully generates non-random XAI heat maps whilst achieving a validation accuracy of 85% and a validation AUC of 93% – as compared to others who achieve a AUC of 87%. Our results conclude that Guided Backpropagation and VarGrad are better at explaining high-level image features whereas Grad-CAM and Sobol Attribution are better at explaining low-level ones. This makes the two groups of XAI methods good complements to each other. Images of Microsatellite Insta- bility (MSI) with high differentiation are more difficult to analyse regardless of which XAI is used, probably due to exhibiting less regularity. Regardless of this drawback, our assessment is that XAI can be used as a useful hypotheses generating tool for research in medicine. Our results indicate that our CNN utilizes the same features as our basic pathology annotations when classifying MSI – with some additional features of basic pathology missing – features which we successfully are able to generate new hypotheses with.