NNAN: Nearest Neighbor Attention Network to Predict Drug-Microbe Associations.

Many drugs can be metabolized by human microbes; the drug metabolites would significantly alter pharmacological effects and result in low therapeutic efficacy for patients. Hence, it is crucial to identify potential drug-microbe associations (DMAs) before the drug administrations. Nevertheless, traditional DMA determination cannot be applied in a wide range due to the tremendous number of microbe species, high costs, and the fact that it is time-consuming. Thus, predicting possible DMAs in computer technology is an essential topic. Inspired by other issues addressed by deep learning, we designed a deep learning-based model named Nearest Neighbor Attention Network (NNAN). The proposed model consists of four components, namely, a similarity network constructor, a nearest-neighbor aggregator, a feature attention block, and a predictor. In brief, the similarity block contains a microbe similarity network and a drug similarity network. The nearest-neighbor aggregator generates the embedding representations of drug-microbe pairs by integrating drug neighbors and microbe neighbors of each drug-microbe pair in the network. The feature attention block evaluates the importance of each dimension of drug-microbe pair embedding by a set of ordinary multi-layer neural networks. The predictor is an ordinary fully-connected deep neural network that functions as a binary classifier to distinguish potential DMAs among unlabeled drug-microbe pairs. Several experiments on two benchmark databases are performed to evaluate the performance of NNAN. First, the comparison with state-of-the-art baseline approaches demonstrates the superiority of NNAN under cross-validation in terms of predicting performance. Moreover, the interpretability inspection reveals that a drug tends to associate with a microbe if it finds its top-