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# SignalP 6.0 — Research Notes

Research notes on **SignalP 6.0**, the DTU Health Tech tool that predicts signal
peptides and their cleavage sites across all domains of life using a protein
language model. Compiled 2026-07-14 from the DTU service page, the *Nature
Biotechnology* paper, the PMC full text, and the `fteufel/signalp-6.0` repository.

**Source clip in this vault:** [[2026-07-15_182916_serviceshealthtechdtudk_SignalP-6.0]]
**Downloaded assets:** `papers/…SignalP-6.0_*.pdf`, `raw/…SignalP-6.0/`

## One-line summary

SignalP 6.0 is the first tool that predicts **all five known signal-peptide
types** in one model. It couples a 30-layer BERT protein language model
(ProtBERT, pretrained on UniRef100) to a conditional random field (CRF) decoder
that labels every residue, so it also returns the **cleavage site** and the
**n-/h-/c-region** structure of the signal peptide.

## Contents

| File | What's in it |
|------|--------------|
| [01-overview.md](01-overview.md) | What signal peptides are, the five types, why v6.0 matters |
| [02-architecture.md](02-architecture.md) | Model architecture, training data, cross-validation |
| [03-usage.md](03-usage.md) | Web server + standalone CLI: install, arguments, outputs |
| [04-benchmarks-and-context.md](04-benchmarks-and-context.md) | Performance vs SignalP 5.0, limitations, related tools, references |
| [05-build-notes.md](05-build-notes.md) | Result of cloning + building the GitHub repo (2026-07-14) |
| [06-retraining-cost.md](06-retraining-cost.md) | What it would cost to remake the weights ourselves (fine-tune, not pretrain) |

## Fast facts

- **Developers:** Teufel, Almagro Armenteros, Nielsen et al. — DTU Health Tech / Univ. of Copenhagen / Stockholm Univ.
- **Paper:** *Nature Biotechnology* **40**(7):1023–1025 (2022). DOI [10.1038/s41587-021-01156-3](https://doi.org/10.1038/s41587-021-01156-3). Preprint: bioRxiv 2021.06.09.447770.
- **Web server:** https://services.healthtech.dtu.dk/services/SignalP-6.0/ (free; ≤1000 proteins/job)
- **Code:** https://github.com/fteufel/signalp-6.0 · **Mirror:** https://dtu.biolib.com/SignalP-6
- **License:** free for academic use; commercial use requires a license.
- **Correspondence:** Henrik Nielsen (DTU Health Tech).

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