Abstract
Drug sensitivity is essential for identifying effective treatments. Meanwhile, circular RNA (circRNA) has potential in disease research and therapy. Uncovering the associations between circRNAs and cellular drug sensitivity is crucial for understanding drug response and resistance mechanisms. In this study, we proposed DeepHeteroCDA, a novel circRNA-drug sensitivity association prediction method based on multi-scale heterogeneous network and graph attention mechanism. We first constructed a heterogeneous graph based on drug-drug similarity, circRNA-circRNA similarity, and known circRNA-drug sensitivity associations. Then, we embedded the 2D structure of drugs into the circRNA-drug sensitivity heterogeneous graph and use graph convolutional networks (GCN) to extract fine-grained embeddings of drug. Finally, by simultaneously updating graph attention network for processing heterogeneous networks and GCN for processing drug structures, we constructed a multi-scale heterogeneous network and use a fully connected layer to predict the circRNA-drug sensitivity associations. Extensive experimental results highlight the superior of DeepHeteroCDA. The visualization experiment shows that DeepHeteroCDA can effectively extract the association information. The case studies demonstrated the effectiveness of our model in identifying potential circRNA-drug sensitivity associations. The source code and dataset are available at https://github.com/Hhhzj-7/DeepHeteroCDA.