HGCPep: Hypergraph Deep Learning Identifies Cancer-associated Non-coding Peptides

Abstract A small peptide encoded by a non-coding RNA (ncRNA), known as a non-coding peptide (ncPEP), is emerging as a critical regulator and biomarker in cancer, holding immense promise for immunotherapy. However, systematic identification of ncPEPs is hampered by computational methods that typically analyze peptides based on sequence alone. This approach overlooks the fundamental biological principle that multiple distinct peptides can be translated from a single ncRNA transcript, thus sharing a common transcriptional origin. Here, we address this limitation by developing HGCPep, a deep learning framework that leverages hypergraphs to model these intrinsic relationships. In our model, each ncRNA is represented as a hyperedge connecting the cohort of peptides it encodes, thereby enriching peptide feature representations with transcriptional context. We demonstrate that HGCPep, which integrates a hypergraph neural network with a convolutional neural network, outperforms state-of-the-art methods in identifying cancer-associated ncPEPs. Furthermore, dimensionality reduction of the learned embeddings reveals distinct clustering of ncPEPs by cancer type, illustrating how the model effectively deciphers complex biological associations. Our work introduces a new method for ncPEPs analytics and provides a powerful tool for discovering novel therapeutic targets in oncology. The dataset and source code of our proposed method can be found via https: //github. com/Longwt123/HGCPepGithub.