Jul 2026· IEEE transactions on computational biology and bioinformatics· Vol PP· 0 citations
Medicine
TL;DR
A novel GNN framework, APKAGN, designed for predicting miRNA-disease associations significantly enhances the accuracy of MDAs prediction, offering a powerful tool for investigating disease mechanisms and identifying biomarkers.
Abstract
MicroRNAs (miRNAs) are critical regulators in biological processes such as cell proliferation, differentiation, and apoptosis, with their aberrant expression strongly linked to a range of complex diseases. Because traditional experimental methods for predicting miRNA-disease associations (MDAs) are both time-intensive and costly, computational models offer an efficient alternative. Graph neural networks (GNNs) have shown promise in MDAs prediction. However, existing models often suffer from limitations, including inadequate neighborhood information aggregation, inflexible propagation schemes, and an imbalance between global and local information. To address these issues, this paper presents a novel GNN framework, APKAGN, designed for predicting miRNA-disease associations. APKAGN enhances performance through three innovative mechanisms: 1) Adaptive local propagation, leveraging a gated recursion module to dynamically adjust propagation depth while employing residual connections to preserve multi-scale features. 2) Multi-subspace global aggregation, capturing global topology information via multi-dimensional projection and density-aware KNN selection. 3) Dynamic feature fusion, integrating local and global representations using an attention-based gating mechanism. Evaluated on the updated HMDD v3.2 dataset across multiple independent random seeds, APKAGN achieved an outstanding average AUC of 95.09%, an accuracy of 88.23%, and an F1-score of 88.34%, outperforming seven state-of-the-art baseline models. Case studies on lymphoma, prostate, and breast tumors further demonstrated the predictive performance of the proposed model, with 26, 25, and 27 of the top 30 predicted miRNAs validated in the dbDEMC and miR2Disease databases, respectively. By leveraging adaptive propagation and dynamic KNN mechanisms, APKAGN significantly enhances the accuracy of MDAs prediction, offering a powerful tool for investigating disease mechanisms and identifying biomarkers.
GCN-XGB is a novel hybrid computational framework that integrates a two-layer Graph Convolutional Network with Extreme Gradient Boosting to improve the accuracy of miRNA-disease association prediction and is suggested to be a powerful and reliable tool for identifying potential disease-related miRNAs and prioritizing candidates for experimental validation.
Jie Zhou, Peishen Yan, Jia Qu et al.· Journal of Mechanics in Medi...· 0 citations
MRGBMDAT, a multi-relational graph encoder network with bilinear fusion for miRNA-disease association type prediction significantly outperforms five state-of-the-art methods across multiple evaluation metrics, exhibiting strong discriminative power and generalization capability.
Y. Sun, Wenjing Su, Siqi Zhu et al.· Bioinformatics· 0 citations
MicroRNA (miRNA) dysregulation is a crucial pathogenic factor that extensively participates in the occurrence and progression of various human diseases, especially cancers. Identifying unknown miRNA–disease connections is essential for understanding disease pathogenesis and improving clinical treatment strategies. Traditional biological experiments are often expensive and technically restricted, so computational prediction has become a widely used auxiliary research tool. In this study, we develop a novel predictive model called Attribute-Aware Message Passing Graph Convolutional Network (AAMPGCN) to identify potential miRNA–disease associations. The advantage of AAMPGCN lies in integrating miRNA and disease attribute information into the message-passing process: it partitions the miRNA–disease heterogeneous graph that incorporates miRNA functional similarity, disease semantic similarity, and Gaussian interaction kernel similarity into attribute-homogeneous subgraphs, while restricting high-order message propagation within each subgraph. This mechanism effectively filters cross-attribute noise, preserves the discriminability of miRNA and disease embeddings during deep convolution, and is thus well-adapted to miRNA–disease heterogeneous networks. The AAMPGCN prioritizes miRNA and disease attributes, aggregating messages specifically among nodes with similar attribute characteristics that are relevant to miRNA–disease interactions. Experimental results show that the AAMPGCN model achieves AUC and AUPR values of 94.06 and 93.52 on the HMDD2.0 dataset, which outperforms existing methods. The proposed AAMPGCN provides a new and effective method for miRNA–disease association prediction, and also offers theoretical support for the research on disease molecular mechanisms and the screening of clinical therapeutic targets.
Peng Qin, Jiyong An· International Journal of Mol...· 0 citations
A novel computational framework based on network fusion and matrix completion for miRNA-disease association prediction, which integrates heterogeneous biological information, including miRNA-disease, lncRNA-disease, and miRNA-lncRNA associations, together with disease semantic similarity and miRNA/lncRNA functional similarity is proposed.
A. Toprak· Journal of Computer-Aided Mo...· 0 citations
Drive by the rapid envolution of deep-learning techniques, a large body of biological experiments bas has uncovered extensive associations between microRNAs (miRNAs) and complex human diseases, hig- hlighting the pivotal roles of miRNAs in pathogenesis. Elucidating these associations is essential for understanding disease mechanisms and developing preventive strategies. Traditional wet-lab validati- on, however, is notoriously labor- and resource-intensive, creating an urgent demand for efficient computational tools that can prioritize the most promising miRNA–disease candidates. Existing predictors predominantly rely on a single category of handcrafted features, thereby overlooking the complementary information embedded in multiple, heterogeneous data sources. Although a few recent attempts integrate diverse features, they usually exploit only a limited subset and fail to capture the intricate, non-linear relationships among them. To address these limitations, we propose MFCAMNet, a Multi-Feature fusion and Cross-Self-Attention model for MiRNA–Disease association prediction. Firstly, we construct multiple similarity matrices and employ two independent autoencoders with multi-source feature attention to obtain deep features of miRNA and disease to extract the inherent relationships between multiple features. Secondly, the proposed model employs element-level addition, element-level multiplication, and concatenation operations to generate miRNA-disease pair features with rich information. Finally, we use the encoder structure of the transformer to fuse the three deep features and predict all potential miRNA disease associations. We conducted comprehensive evaluations on the public HMDD v2.0 and HMDD v3.2 benchmark datasets. MFCAMNet achieved average AUCs of 0.9455 and 0.9420 under 5-fold and 10-fold cross-validation on HMDD v2.0, respectively, and an AUC of 0.9578 under 5-fold cross-validation on HMDD v3.2, outperforming state-of-the-art competitors. Case studies on breast, esophageal, and lung cancers further corroborate the reliability and practical utility of the proposed method.