Universal Biological Sequence Reranking for Improved De Novo Peptide Sequencing
preprint · arXiv · 2025
| Date | 2025-05-23 |
| Type | preprint |
| Venue | arXiv |
| Publisher | arXiv |
| Contribution | post-processor |
| DOI | 10.48550/arXiv.2505.17552 |
| Citations (OpenAlex) | 0 |
Peer-reviewed version: Universal Biological Sequence Reranking for Improved De Novo Peptide Sequencing (2025-07-13, ICML 2025)
Abstract
De novo peptide sequencing is a critical task in proteomics. However, the performance of current deep learning-based methods is limited by the inherent complexity of mass spectrometry data and the heterogeneous distribution of noise signals, leading to data-specific biases. We present RankNovo, the first deep reranking framework that enhances de novo peptide sequencing by leveraging the complementary strengths of multiple sequencing models. RankNovo employs a list-wise reranking approach, modeling candidate peptides as multiple sequence alignments and utilizing axial attention to extract informative features across candidates. Additionally, we introduce two new metrics, PMD (Peptide Mass Deviation) and RMD (residual Mass Deviation), which offer delicate supervision by quantifying mass differences between peptides at both the sequence and residue levels. Extensive experiments demonstrate that RankNovo not only surpasses its base models used to generate training candidates for reranking pre-training, but also sets a new state-of-the-art benchmark. Moreover, RankNovo exhibits strong zero-shot generalization to unseen models whose generations were not exposed during training, highlighting its robustness and potential as a universal reranking framework for peptide sequencing. Our work presents a novel reranking strategy that fundamentally challenges existing single-model paradigms and advances the frontier of accurate de novo sequencing. Our source code is provided on GitHub.
Methods and tools
- RankNovo: Universal reranking
Cites (20)
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Cited by (5)
- LIPNovo+: Self-Reflective Latent Imputation for Robust De Novo Peptide Sequencing (2026) crossref
- Bidirectional Representations Augmented Autoregressive Biological Sequence Generation (2025) semanticscholar
- Protein Language Model-Aligned Spectra Embeddings for De Novo Peptide Sequencing (2025) semanticscholar
- MassNet: billion-scale AI-friendly mass spectral corpus enables robust de novo peptide sequencing (2025) both
- Curriculum Learning for Biological Sequence Prediction: The Case of De Novo Peptide Sequencing (2025) semanticscholar