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Published on: March 1, 2024
Predicting miRNA-disease associations based on graph random propagation network and attention network
Tangbo Zhong1,2, Zhengwei Li1,2, Zhu-Hong You3
1Engineering Research Center of Mine Digitalization of Ministry of Education, China University of Mining and Technology, Xuzhou, China.
Abstract:
Numerous experiments have demonstrated that abnormal expression of microRNAs (miRNAs) in organisms is often accompanied by the emergence of specific diseases. The research of miRNAs can promote the prevention and drug research of specific diseases. However, there are still many undiscovered links between miRNAs and diseases, which greatly limits the research of miRNAs. Therefore, for exploring the unknown miRNA-disease associations, we combine the graph random propagation network based on DropFeature with attention network to propose a novel deep learning model to predict the miRNA-disease associations (GRPAMDA). Specifically, we firstly construct the miRNA-disease heterogeneous graph based on miRNA-disease association information. Secondly, we adopt DropFeature to randomly delete the features of nodes in the graph and then perform propagation operations to enhance the features of miRNA and disease nodes. Thirdly, we employ the attention mechanism to fuse the features of random propagation by aggregating the enhanced neighbor features of miRNA and disease nodes. Finally, miRNA-disease association scores are generated by a fully connected layer. The average area under the curve of GRPAMDA model based on 5-fold cross-validation is 93.46% on HMDD v2.0. Case studies of esophageal tumors, lymphomas and prostate tumors show that 48, 47 and 46 of the top 50 miRNAs associated with these diseases are confirmed by dbDEMC and miR2Disease database, respectively. In short, the GRPAMDA model can be used as a valuable method to study miRNA-disease associations.
Insights
This study introduces GRPAMDA, a novel deep learning model for predicting microRNA-disease associations. GRPAMDA enhances disease research by uncovering new links between microRNAs (miRNAs) and diseases.
Area of Science:
- Bioinformatics
- Computational Biology
- Genomics
Background:
- Abnormal microRNA (miRNA) expression is linked to various diseases, making miRNA research crucial for disease prevention and drug development.
- Numerous undiscovered associations between miRNAs and diseases hinder comprehensive research and therapeutic advancements.
Purpose of the Study:
- To develop a novel deep learning model, GRPAMDA, for predicting unknown miRNA-disease associations.
- To enhance the understanding of miRNA roles in disease pathogenesis.
Main Methods:
- Constructed a miRNA-disease heterogeneous graph using known association data.
- Applied DropFeature and graph random propagation to enhance node features.
- Utilized an attention mechanism to fuse propagated features and aggregate neighbor information.
- Generated miRNA-disease association scores using a fully connected layer.
Main Results:
- The GRPAMDA model achieved an average area under the curve of 93.46% on the HMDD v2.0 dataset via 5-fold cross-validation.
- Case studies demonstrated high accuracy in identifying disease-associated miRNAs for esophageal tumors, lymphomas, and prostate tumors, with many validated by external databases.
- The model effectively predicts novel miRNA-disease associations.
Conclusions:
- GRPAMDA offers a valuable computational method for exploring and predicting miRNA-disease associations.
- The model's performance highlights its potential to accelerate miRNA-related disease research and therapeutic discovery.
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