A multi-view feature fusion framework with interpretable graph convolution for predicting microbe-drug associations.

Abstract

Predicting associations between human microbes and drugs (MDA) is a critical step in drug development and precision medicine. Although various computational approaches have been proposed, many existing models still struggle to reveal the key features and interaction mechanisms that drive their predictions, and their decision processes remain difficult to interpret and validate biologically. To address these limitations, we propose IDEAL (Interpretability-Driven Evolvable Attentive Learning for Microbe-Drug Association), a multi-view framework that integrates drug network topological attributes, BERT-encoded drug semantics, drug fingerprints, microbe genome sequence attributes, BERT-encoded microbe semantics, and microbe metabolic pathway attributes. We further introduce GNNExplainer into the graph convolutional network (GCN) pipeline to identify influential drug-microbe relations and feed the resulting structural signal back into graph refinement. In addition, we employ Elastic Weight Consolidation (EWC) to support parameter-efficient adaptation when biological data grow over time while mitigating catastrophic forgetting. Extensive experiments on three public datasets demonstrate that the proposed method achieves strong predictive performance, offers interpretable structural explanations, and provides a practical transfer-learning route for evolving MDA benchmarks. The source code for our model is publicly available at https://github.com/Luoxidu02/IDEAL.