Dual-Stream Heterogeneous Graph Neural Network Based on Zero-Shot Embeddings for Predicting miRNA-Drug Sensitivity

MicroRNAs (miRNAs) are a class of non-coding RNA molecules that have been shown to be closely associated with the sensitivity of chemotherapeutic drugs in cancer treatment. Given the high cost and extended duration of traditional biological experiments, there is an urgent need to develop computational models to predict the sensitivity scores between miRNAs and drugs. In this study, we proposed a dual-stream graph neural network method based on Zero-Shot Embeddings, named DSHGZS, to explore the potential sensitivity scores between miRNAs and drugs. DSHGZS first constructs two heterogeneous graphs with different isomorphic subgraphs based on zero-shot embeddings obtained from large language models (LLMs) and known miRNA-drug association data. It then utilized the enhanced LLM-derived node feature representations, embedding them into the layer feature learning process of the two heterogeneous graphs to generate high-quality vector representations of miRNAs and drugs. The learned high-quality feature embeddings are subsequently used in a segmented inner product decoder to evaluate the sensitivity association scores between miRNAs and drugs. To address the model’s excessive reliance on high-quality feature representations, we employed PCA to extract the core representations of the LLM-derived node features for data augmentation. Case studies demonstrated that DSHGZS is an effective tool for predicting potential sensitivity scores between miRNAs and drugs.