HMA-GCA: hybrid manifold augmentation and gated cross-attention for circRNA-miRNA interaction prediction

Motivation: Circular RNAs (circRNAs) interact with microRNAs (miRNAs) to regulate gene expression and influence disease progression. However, traditional models tend to overlook the significant contributions of certain features when dealing with diverse sequence information, resulting in the inability to capture some deep topological structures and thus leaving room for improvement in prediction performance. Results: We propose HMA-GCA, a novel framework that integrates hybrid manifold augmentation and gated cross-attention for CMI prediction. The model first constructs multi-scale descriptors by combining sequence-derived features (K-mer, CTD, Doc2Vec) and topological features (Role2Vec, node degree, neighborhood proximity). It then applies PCA for global linear projection and UMAP for local nonlinear manifold learning, enhancing feature representations while preserving intrinsic data geometry. A channel-wise gated cross-attention mechanism dynamically controls the injection of miRNA information into circRNA representations. Extensive experiments on three benchmark datasets show that HMA-GCA consistently outperforms state-of-the-art methods across multiple metrics. To ensure interpretability, we conducted SHAP analysis to quantify the contribution of each feature type, revealing that sequence-derived features and topological similarities are the most influential. Ablation studies confirm the necessity of each module, while case studies demonstrate that top-ranked predictions are supported by literature evidence. Overall, HMA-GCA not only achieves state-of-the-art predictive performance but also provides interpretable insights into the molecular features. Availability and implementation: The source code and data are freely available at https://github.com/Lixunwind/Prediction-circ-mi-by-Gate.git. The implementation is based on Python and the required dependencies are listed in the repository.