Prediction of microbe-drug associations using a CNN-Bernoulli random forest model

Antibiotics play a critical role in treating microbial infections. However, their widespread use has contributed to the growing problem of microbial resistance. Addressing this challenge requires the identification of new microbe-drug associations to support the development of novel therapeutic strategies. Since traditional wet-lab experiments are time-consuming and costly, computational models offer an efficient alternative for discovering potential applications of existing drugs against previously untested microbes. These models can facilitate the identification of novel microbe-drug associations and help counteract resistance mechanisms.

This study proposes a novel computational model: convolutional neural network with Bernoulli random forest for Microbe-Drug Association prediction (CNNBRFMDA). The model constructs feature vectors for all microbe-drug pairs based on known associations, microbe similarity, and drug similarity. A subset of these vectors is randomly selected to form the training set. A convolutional neural network (CNN) is then used to reduce the dimensionality of all feature vectors, including those in the training set. The reduced training set is subsequently used to train a Bernoulli random forest (BRF) to predict potential microbe-drug associations. The innovation of CNNBRFMDA lies in its integration of CNN for nonlinear feature extraction and BRF for robust prediction. This approach enhances computational efficiency and improves the model's ability to capture complex patterns, thereby increasing the precision and interpretability of drug response predictions. The dual use of the Bernoulli distribution in BRF ensures algorithmic consistency and contributes to superior performance.

The model was evaluated using five-fold cross-validation on the Microbe-Drug Association Database (MDAD) and abiofilm datasets. CNNBRFMDA achieved mean AUC scores of 0.9017 ± 0.0032 (MDAD) and 0.9146 ± 0.0041 (abiofilm). Two case studies further validated the model's reliability: 41 of the top 50 predicted microbes associated with ciprofloxacin and 38 of the top 50 associated with moxifloxacin were confirmed through literature review.