LncPNdeep: A long non-coding RNA classifier based on large language model with peptide and nucleotide embedding.

Abstract

Accurate classification of long non-coding RNAs (lncRNAs) is essential for transcriptome annotation and understanding gene regulation. Existing computational methods predominantly rely on nucleotide sequence features, frequently overlooking biologically relevant peptide signals encoded within lncRNAs. To overcome this limitation, we developed LncPNdeep, an integrative deep learning framework that combines nucleotide and peptide embeddings extracted via masked language models, specifically utilizing contextual representations from BigBird, Longformer, and ProtTrans. By fusing both features in a concatenated neural architecture, LncPNdeep robustly captures complex sequence relationships and improves discrimination between lncRNAs and coding RNAs. Benchmarking on the human transcriptome achieved state-of-the-art performance with 97.1% accuracy, surpassing established lncRNA classification tools and baseline machine learning models. LncPNdeep also demonstrated superior generalization ability across cross-species datasets, maintaining consistently high accuracy and F1 scores. Permutation analysis highlighted the pivotal role of peptide embeddings, especially Average Peptide Embedding, in model performance, while t-SNE visualizations confirmed that integrating multiple embeddings markedly enhances the separation of lncRNAs from coding RNAs. These results position LncPNdeep as a versatile and powerful tool for transcriptomic research, facilitating lncRNA discovery, biomarker identification, and comparative genomics. The model and instructions are freely available at https://github.com/yatoka233/LncPNdeep.