π-PrimeNovo: an accurate and efficient non-autoregressive deep learning model for de novo peptide sequencing

• Published in: Nature communications 2025-01, Vol.16 (1), p.267-16, Article 267
• Main Authors: Zhang, Xiang, Ling, Tianze, Jin, Zhi, Xu, Sheng, Gao, Zhiqiang, Sun, Boyan, Qiu, Zijie, Wei, Jiaqi, Dong, Nanqing, Wang, Guangshuai, Wang, Guibin, Li, Leyuan, Abdul-Mageed, Muhammad, Lakshmanan, Laks V. S., He, Fuchu, Ouyang, Wanli, Chang, Cheng, Sun, Siqi
• Format: Article
• Language: English
• Subjects: 631/114/1305; 631/114/2784; 631/45/475; Accuracy; Algorithms; Biological research; Databases, Protein; Deep Learning; Humanities and Social Sciences; Humans; Inference; Mass spectrometry; Mass spectroscopy; multidisciplinary; Peptides; Peptides - chemistry; Peptides - metabolism; Phosphopeptides - chemistry; Phosphopeptides - metabolism; Post-translation; Protein Processing, Post-Translational; Proteomics; Proteomics - methods; Science; Science (multidisciplinary); Sequence Analysis, Protein - methods; Software; Tandem Mass Spectrometry - methods
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-024-55021-3

Peptide sequencing via tandem mass spectrometry (MS/MS) is essential in proteomics. Unlike traditional database searches, deep learning excels at de novo peptide sequencing, even for peptides missing from existing databases. Current deep learning models often rely on autoregressive generation, which suffers from error accumulation and slow inference speeds. In this work, we introduce π -PrimeNovo, a non-autoregressive Transformer-based model for peptide sequencing. With our architecture design and a CUDA-enhanced decoding module for precise mass control, π -PrimeNovo achieves significantly higher accuracy and up to 89x faster inference than state-of-the-art methods, making it ideal for large-scale applications like metaproteomics. Additionally, it excels in phosphopeptide mining and detecting low-abundance post-translational modifications (PTMs), marking a substantial advance in peptide sequencing with broad potential in biological research. Peptide sequencing is critical to the advancement of proteomics research. Here, the authors present π- PrimeNovo, a non-autoregressive deep learning model that achieves high accuracy and up to 89x faster sequencing. This enables large-scale sequencing and multiple downstream applications.