A procedure for controlling the false discovery rate of de novo peptide sequencing
preprint · bioRxiv · 2025
preprint · bioRxiv · 2025. Justin Sanders et al. De novo sequencing is a powerful method for identifying peptides from mass spectrometry proteomics…
| Date | 2025-09-17 |
| Type | preprint |
| Venue | bioRxiv |
| Publisher | Cold Spring Harbor Laboratory |
| Contribution | post-processor |
| DOI | 10.1101/2025.09.12.675837 |
| Citations (OpenAlex) | 0 |
Abstract
De novo sequencing is a powerful method for identifying peptides from mass spectrometry proteomics experiments without the use of a protein database. However, applications of de novo sequencing are currently severely limited by the lack of a reliable procedure for controlling the false discovery rate (FDR). Here, we introduce an FDR control procedure for the de novo setting which is at least as powerful as database search, give empirical evidence that it is statistically valid, and demonstrate its utility on a set of common de novo applications.
Methods and tools
- De novo FDR control procedure: False discovery rate control for the de novo setting, where target-decoy competition does not apply: reported to be at least as powerful as database search, with empirical evidence of statistical validity on a set of common de novo applications.
Data used
- A comprehensive LFQ benchmark dataset to validate data analysis pipelines on modern day acquisition strategies in proteo — as deposited · PXD028735
- A mass-tolerant database search identifies a large proportion of unassigned spectra in shotgun proteomics as modified pe — as deposited · PXD001468
- Assessing protein sequence database suitability using de novo sequencing — as deposited · PXD015083
- PXD066485 — as deposited · PXD066485
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