Pep-PU-GAN: Positive-Unlabeled Adversarial Learning for Peptide Function Prediction

Abstract

Peptide classification remains challenging in bioinformatics because of limited labeled data, particularly the scarcity of verified negative examples, and the complex relationship between amino acid sequences and biological functions. This study introduces Pep-PU-GAN, a deep learning framework that combines positive-unlabeled (PU) learning, generative adversarial networks (GANs), and graph neural networks (GNNs) for peptide classification. Peptides are represented as sequence-derived residue graphs, with amino acids as nodes and edges connecting adjacent residues, enabling attention-based message passing over local neighborhoods. The architecture includes a generator that produces synthetic peptide embeddings in encoder space and a dual-function discriminator that distinguishes real from synthetic embeddings while performing PU classification. Training uses a custom loss integrating non-negative PU (nnPU) risk estimation with adversarial objectives. A self-training mechanism further incorporates high-confidence synthetic positive embeddings to augment the training set and improve performance. Evaluated on neuropeptide classification using 4,049 positive neuropeptides and 8,558 unlabeled peptides, Pep-PU-GAN outperformed baseline models, achieving an F1 score of 0.93 and an AUROC of 0.98 on an independent held-out benchmark. Pep-PU-GAN provides a promising approach for peptide classification tasks with scarce labeled and abundant unlabeled data, with potential applications in computational biology and drug discovery.