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

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, the systematic identification of ncPEPs remains a challenge because existing computational methods typically analyze peptides based on sequence alone. Sequence-only analysis overlooks the fundamental biological principle that multiple distinct peptides can be translated from a single non-coding RNA 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 set 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 ncPEP analysis 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/HGCPep_Github.