Prioritizing peptides for targeted mass spectrometry experiments using deep learning
- 1University of Washington
Abstract
One critical step in any targeted mass spectrometry experiment is selecting, from each protein of interest, a small number of peptides that respond well in the mass spectrometer and can serve as reliable proxies for protein quantification. Existing methods select target peptides either by relying on prior empirical measurements, limiting their applicability to previously observed peptides, or using machine learning to predict peptide behavior from sequence alone. However, current machine learning tools suffer from various limitations, including using detectability as an indirect proxy for intensity, relying on small training sets, or ignoring the precursor charge state. In this study, we introduce Bromo, a transformer-based deep learning model that ranks peptide precursors from a given protein by their relative response, taking charge state into account. Trained on millions of annotated peptide pairs derived from large-scale, publicly available data-independent acquisition mass spectrometry data, Bromo consistently outperforms existing sequence-based methods across diverse, independent datasets. Furthermore, we show that fine-tuning Bromo on experiment-specific data can account for differences in sample preparation, sample matrix, and instrument platform, all of which influence which peptides serve as optimal targets. This adaptability makes Bromo a practical tool for selecting target peptides for selected reaction monitoring and parallel reaction monitoring assay development across a wide range of experimental conditions.
Versions
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BibTeX
@misc{sonthalia2026prioritizing,
title = {{Prioritizing peptides for targeted mass spectrometry experiments using deep learning}},
author = {S. Sonthalia and B. Wen and P. Dasgupta and C. Hsu and M. J. MacCoss and W. S. Noble},
howpublished = {bioRxiv},
year = {2026},
month = may,
doi = {10.64898/2026.05.21.727053},
url = {https://www.biorxiv.org/content/10.64898/2026.05.21.727053v2},
note = {CC BY},
}
RIS
TY - UNPB
TI - Prioritizing peptides for targeted mass spectrometry experiments using deep learning
AU - S. Sonthalia
AU - B. Wen
AU - P. Dasgupta
AU - C. Hsu
AU - M. J. MacCoss
AU - W. S. Noble
PY - 2026
DA - 2026/05/21
PB - bioRxiv
DO - 10.64898/2026.05.21.727053
UR - https://www.biorxiv.org/content/10.64898/2026.05.21.727053v2
AB - One critical step in any targeted mass spectrometry experiment is selecting, from each protein of interest, a small number of peptides that respond well in the mass spectrometer and can serve as reliable proxies for protein quantification. Existing methods select target peptides either by relying on prior empirical measurements, limiting their applicability to previously observed peptides, or using machine learning to predict peptide behavior from sequence alone. However, current machine learning tools suffer from various limitations, including using detectability as an indirect proxy for intensity, relying on small training sets, or ignoring the precursor charge state. In this study, we introduce Bromo, a transformer-based deep learning model that ranks peptide precursors from a given protein by their relative response, taking charge state into account. Trained on millions of annotated peptide pairs derived from large-scale, publicly available data-independent acquisition mass spectrometry data, Bromo consistently outperforms existing sequence-based methods across diverse, independent datasets. Furthermore, we show that fine-tuning Bromo on experiment-specific data can account for differences in sample preparation, sample matrix, and instrument platform, all of which influence which peptides serve as optimal targets. This adaptability makes Bromo a practical tool for selecting target peptides for selected reaction monitoring and parallel reaction monitoring assay development across a wide range of experimental conditions.
ER -