Documented workflows
Published software workflows and their original methodological context. Check current software documentation for version-specific changes.
De novo structure generation with MSNovelist in SIRIUS
MSNovelist addresses cases where database searching cannot recover the correct structure because the molecule is absent from candidate databases. It uses a SIRIUS molecular formula and CSI:FingerID fingerprint prediction to generate and rank de novo structure candidates, now integrated into the SIRIUS 6 ecosystem.
- Establish molecular formula and MS/MS representation
Use SIRIUS to identify a plausible molecular formula and compute the fragmentation-based representation needed for downstream fingerprint prediction.
- Predict structural fingerprints
Run CSI:FingerID fingerprint prediction to estimate structural properties from the fragmentation spectrum.
- Generate structures with MSNovelist
Generate candidate molecular structures de novo under the constraints of the molecular formula and predicted structural fingerprint.
- Rank, inspect, and validate candidates
Review generated structures and prioritize candidates using chemical plausibility and orthogonal analytical or biological evidence before making identification claims.
Requirements
- A plausible molecular formula and informative MS/MS spectrum; the current MSNovelist implementation is a webservice-backed SIRIUS feature.
Considerations
- Generated structures are hypotheses and require strong orthogonal validation before structural identification.
- The original standalone MSNovelist repository/backend is archived and no longer operative; current users should use the implementation integrated into SIRIUS 6.
Stravs MA, Dührkop K, Böcker S, Zamboni N. MSNovelist: de novo structure generation from mass spectra. Nature Methods 19, 865–870 (2022).
Read the source methodOverview
MSNovelist generates candidate chemical structures de novo from a molecular formula and predicted molecular fingerprint derived from MS/MS data. The original standalone implementation and backend are end-of-life; since 2024, a retrained and expanded MSNovelist implementation has been integrated into SIRIUS 6 and is accessed through the SIRIUS webservice workflow. It is designed to propose structures beyond the contents of conventional structure databases.
What can this tool do?
Common uses
- Generate de novo molecular-structure candidates when database search cannot provide a satisfactory candidate.
- Explore plausible structures from SIRIUS molecular formulas and CSI:FingerID-predicted fingerprints.
- Prioritize candidate structures for unknown metabolites that are poorly represented in existing structure databases.
Scientific fit
Primary function
Metabolite annotation and identification
Other functions
Machine learning and prediction
Analysis types
Untargeted metabolomics, Metabolite profiling
MS level
MS/MS
Acquisition
Data-dependent acquisition (DDA), Targeted MS/MS, General or unspecified acquisition
Ion mobility
Ion mobility not required
Data compatibility
Inputs
Mass spectra
Outputs
Molecular structures, Human-readable report
Input formats
mzML, mzXML, MGF, MSP, SIRIUS project with formula and fingerprint predictions
Output formats
CSV or TSV, JSON, SIRIUS generated structure-candidate tables
Scope and considerations
Designed for
- De novo candidate generation from accurate-mass MS/MS data for small molecules.
Not designed for
- Experimental confirmation of a generated structure or its stereochemistry.
Important requirements
- SIRIUS molecular-formula/fingerprint results and access to the SIRIUS webservice.
Considerations
- Generated structures are hypotheses rather than definitive identifications and require substantial orthogonal validation.
- The historical standalone MSNovelist repository is archived; current users should use the implementation integrated into SIRIUS 6.
- A chemically valid generated candidate is a hypothesis; inspect alternative candidates and preserve the molecular formula and prediction settings.
Access and documentation
The current MSNovelist implementation is integrated into SIRIUS 6 and requires SIRIUS webservice access. The linked standalone repository is archived and retained for historical reference.
Evidence and review
Documentation-based editorial pass on 6 September 2026: scope, interpretation limits and practical use reviewed against the linked official documentation and cited literature. Software execution, service availability and developer verification were not assessed.
Core publications
Resource papers, direct updates and tool-specific methods. Selection policy.
- Stravs MA, Dührkop K, Böcker S, et al. MSNovelist: de novo structure generation from mass spectra. Nat Methods 19, 865-870 (2022). doi:10.1038/s41592-022-01486-3
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Entry history
Changes to this catalogue entry, not the tool's software release history. Acceptance and editorial review are separate.
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