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SAGCN: Using Graph Convolutional Network With Subgraph-Aware for circRNA-Drug Sensitivity Identification
Abstract:
Circular RNAs (circRNAs) play a significant role in cancer development and therapy resistance. There is substantial evidence indicating that the expression of circRNAs affects the sensitivity of cells to drugs. Identifying circRNAs-drug sensitivity association (CDA) is helpful for disease treatment and drug discovery. However, the identification of CDA through conventional biological experiments is both time-consuming and costly. Therefore, it is urgent to develop computational methods to predict CDA. In this study, we propose a new computational method, the subgraph-aware graph convolutional network (SAGCN), for predicting CDA. SAGCN first constructs a heterogeneous network composed of circRNA similarity network, drug similarity network, and circRNA-drug bipartite network. Then, a subgraph extractor is proposed to learn the latent subgraph structure of the heterogeneous network using a graph convolutional network. The extractor can capture 1-hop and 2-hop information and then a fusing attention mechanism is designed to integrate them adaptively. Simultaneously, a novel subgraph-aware attention mechanism is proposed to detect intrinsic subgraph structure. The final node feature representation is obtained to make the CDA prediction. Experimental results demonstrate that SAGCN obtained an average AUC of 0.9120 and AUPR of 0.8693, exceeding the performance of the most advanced models under 10-fold cross-validation. Case studies have demonstrated the potential of SAGCN in identifying associations between circRNA and drug sensitivity.
Insights
This study introduces SAGCN, a computational method for predicting circular RNA-drug sensitivity associations (CDA). SAGCN accurately identifies these crucial links, aiding cancer therapy and drug discovery.
Area of Science:
- Bioinformatics
- Computational Biology
- Genomics
Background:
- Circular RNAs (circRNAs) are implicated in cancer development and drug resistance.
- circRNA expression significantly influences cellular drug sensitivity.
- Identifying circRNA-drug sensitivity associations (CDA) is vital for advancing cancer treatment and drug discovery.
Purpose of the Study:
- To address the time-consuming and costly nature of experimental CDA identification.
- To develop an efficient computational method for predicting CDA.
- To propose the subgraph-aware graph convolutional network (SAGCN) for CDA prediction.
Main Methods:
- Constructed a heterogeneous network integrating circRNA similarity, drug similarity, and circRNA-drug bipartite networks.
- Employed a subgraph extractor utilizing graph convolutional networks to learn latent network structures.
- Integrated 1-hop and 2-hop information using a fusing attention mechanism and a novel subgraph-aware attention mechanism.
Main Results:
- The SAGCN model achieved an average AUC of 0.9120 and AUPR of 0.8693.
- SAGCN outperformed existing state-of-the-art models in 10-fold cross-validation.
- Case studies validated SAGCN's capability in identifying circRNA-drug sensitivity links.
Conclusions:
- SAGCN provides an effective computational approach for predicting circRNA-drug sensitivity associations.
- The method offers a valuable tool for accelerating drug discovery and optimizing cancer therapies.
- SAGCN's performance highlights the potential of graph-based deep learning in biological network analysis.

