Kaili Wang

Zhangli Lu, Chuqi Lei, Kaili Wang et al.

Accurate and robust prediction of drug-target interactions (DTIs) plays a vital role in drug discovery. Despite extensive efforts have been invested in predicting novel DTIs, existing approaches still suffer from insufficient labeled data and cold start problems. More importantly, there is currently a lack of studies focusing on elucidating the mechanism of action (MoA) between drugs and targets. Distinguishing the activation and inhibition mechanisms is critical and challenging in drug development. Here, we introduce a unified framework called DTIAM, which aims to predict interactions, binding affinities, and activation/inhibition mechanisms between drugs and targets. DTIAM learns drug and target representations from large amounts of label-free data through self-supervised pre-training, which accurately extracts the substructure and contextual information of drugs and targets, and thus benefits the downstream prediction based on these representations. DTIAM achieves substantial performance improvement over other state-of-the-art methods in all tasks, particularly in the cold start scenario. Moreover, independent validation demonstrates the strong generalization ability of DTIAM. All these results suggested that DTIAM can provide a practically useful tool for predicting novel DTIs and further distinguishing the MoA of candidate drugs. DTIAM, for the first time, provides a unified framework for accurate and robust prediction of drug-target interactions, binding affinities, and activation/inhibition mechanisms.

Kaili Wang, Jose Oramas, Tinne Tuytelaars

Explainable AI (XAI) methods focus on explaining what a neural network has learned - in other words, identifying the features that are the most influential to the prediction. In this paper, we call them "distinguishing features". However, whether a human can make sense of the generated explanation also depends on the perceptibility of these features to humans. To make sure an explanation is human-understandable, we argue that the capabilities of humans, constrained by the Human Visual System (HVS) and psychophysics, need to be taken into account. We propose the {\em human perceptibility principle for XAI}, stating that, to generate human-understandable explanations, neural networks should be steered towards focusing on human-understandable cues during training. We conduct a case study regarding the classification of real vs. fake face images, where many of the distinguishing features picked up by standard neural networks turn out not to be perceptible to humans. By applying the proposed principle, a neural network with human-understandable explanations is trained which, in a user study, is shown to better align with human intuition. This is likely to make the AI more trustworthy and opens the door to humans learning from machines. In the case study, we specifically investigate and analyze the behaviour of the human-imperceptible high spatial frequency features in neural networks and XAI methods.