PepGo: a deep learning and tree search-based model for de novo peptide sequencing
preprint · bioRxiv · 2025
| Date | 2025-02-24 |
| Type | preprint |
| Venue | bioRxiv |
| Publisher | Cold Spring Harbor Laboratory |
| Contribution | algorithm |
| DOI | 10.1101/2025.02.24.640018 |
| Citations (OpenAlex) | 1 |
Abstract
Identifying peptide sequences from tandem mass spectra is a fundamental problem in proteomics. Unlike search-based methods that rely on matching spectra to databases, de novo peptide sequencing determines peptides directly from mass spectra without any prior information. However, the design of models and algorithms for de novo peptide sequencing remains a challenge. Many de novo approaches leverage deep learning but primarily focus on the architecture of neural networks, paying less attention to search algorithms. We introduce PepGo, a de novo peptide sequencing model that integrates Transformer neural networks with Monte Carlo Tree Search (MCTS). PepGo predicts peptide sequences directly from mass spectra without databases, even without prior training. We show that PepGo surpasses existing methods, achieving state-of-the-art performance. To our knowledge, this is the first approach to combine deep learning with MCTS for de novo peptide sequencing, offering a powerful and adaptable solution for peptide identification in proteomics research. Competing Interest Statement The authors have declared no competing interest.
Methods and tools
- PepGo: Tree search-based decoding
Cites (32)
- Sequence-to-sequence translation from mass spectra to peptides with a transformer model (2024) crossref
- Mitigating the missing-fragmentation problem in de novo peptide sequencing with a two-stage graph-based deep learning model (2023) semanticscholar
- DPST: De Novo Peptide Sequencing with Amino-Acid-Aware Transformers (2022) crossref
- Computationally instrument-resolution-independent de novo peptide sequencing for high-resolution devices (2021) semanticscholar
- Peptide Sequencing with Deep Learning (2020) crossref
- Uncovering Thousands of New Peptides with Sequence-Mask-Search Hybrid De Novo Peptide Sequencing Framework (2019) crossref
- Prosit: proteome-wide prediction of peptide tandem mass spectra by deep learning (2019) crossref
- DeepNovoV2: Better de novo peptide sequencing with deep learning (2019) semanticscholar
- De novo peptide sequencing by deep learning (2017) crossref
- UVnovo: A de Novo Sequencing Algorithm Using Single Series of Fragment Ions via Chromophore Tagging and 351 nm Ultraviolet Photodissociation Mass Spectrometry (2016) crossref
- Application of de Novo Sequencing to Large-Scale Complex Proteomics Data Sets (2016) crossref
- Novor: Real-Time Peptide de Novo Sequencing Software (2015) crossref
- MS2PIP: a tool for MS/MS peak intensity prediction (2013) crossref
- UniNovo: a universal tool for de novo peptide sequencing (2013) crossref
- Sequencing-Grade De novo Analysis of MS/MS Triplets (CID/HCD/ETD) From Overlapping Peptides (2013) crossref
- pNovo+: De Novo Peptide Sequencing Using Complementary HCD and ETD Tandem Mass Spectra (2013) crossref
- Antilope—A Lagrangian Relaxation Approach to the de novo Peptide Sequencing Problem (2012) crossref
- pNovo: De novo Peptide Sequencing and Identification Using HCD Spectra (2010) crossref
- A high-throughput de novo sequencing approach for shotgun proteomics using high-resolution tandem mass spectrometry (2010) crossref
- De novo peptide sequencing by tandem MS using complementary CID and electron transfer dissociation (2009) crossref
- DirecTag: Accurate Sequence Tags from Peptide MS/MS through Statistical Scoring (2008) crossref
- MSNovo: A Dynamic Programming Algorithm for de Novo Peptide Sequencing via Tandem Mass Spectrometry (2007) crossref
- De Novo Peptide Identification via Tandem Mass Spectrometry and Integer Linear Optimization (2007) crossref
- NovoHMM: A Hidden Markov Model for de Novo Peptide Sequencing (2005) crossref
- AUDENS: A Tool for Automated Peptide de Novo Sequencing (2005) crossref
- PepNovo: de novo peptide sequencing via probabilistic network modeling (2005) crossref
- De Novo Peptide Sequencing Based on a Divide-and-Conquer Algorithm and Peptide Tandem Spectrum Simulation (2004) crossref
- GutenTag: High-Throughput Sequence Tagging via an Empirically Derived Fragmentation Model (2003) crossref
- PEAKS: powerful software for peptide de novo sequencing by tandem mass spectrometry (2003) crossref
- Searching Sequence Databases via De Novo Peptide Sequencing by Tandem Mass Spectrometry (2002) crossref
- A Dynamic Programming Approach to De Novo Peptide Sequencing via Tandem Mass Spectrometry (2001) crossref
- De novo peptide sequencing via tandem mass spectrometry (1999) crossref