How much of natural-product chemical space has a reference spectrum? An open audit of GNPS, MassBank and MoNA against COCONUT and LOTUS
Year: 2026
Type: preprint
Abstract: Annotation of untargeted mass spectrometry data rests on reference MS/MS spectra, yet how much of documented natural-product (NP) chemistry actually has one has been asserted rather than measured. We present SPECGAP, an open, dependency-free engine that joins NP structure databases to spectral libraries on InChIKey identity and reports two quantities with explicit denominators: structural coverage, the share of reference structures with at least one experimental MS2 spectrum, and name-recoverability, the share of spectra whose declared compound name reconciles with the reference database. Applied to the complete open experimental layer—2,745,226 MS2 spectra from MassBank, MoNA and GNPS (280,024 distinct compounds)—against 738,823 COCONUT and 227,298 LOTUS structures, SPECGAP finds that 90.34% of COCONUT and 88.16% of LOTUS have no spectrum even when stereochemistry is ignored (exact-key coverage 2.86% and 5.08%). Coverage grows sublinearly: a 19.7-fold increase in spectra bought a 2.63-fold increase in covered structures, an elasticity of 0.32, because only 7.5% of the compounds in the layer are COCONUT natural products. Composition outweighs size: GNPS added 7.4-fold fewer new compounds than MoNA but a 5.9-fold higher NP hit rate (18.8% versus 3.2%). Both measures depend on the reference database: LOTUS is 3.25-fold smaller than COCONUT yet 1.78-fold better covered, while the same spectra recover 69.54% of their names against COCONUT and 36.17% against LOTUS. On the one run with archived match-level detail, 12.1% of recoveries came from fuzzy name matching; exact matching alone gives 31.82%, and we show the fuzzy rule can accept congener names. Library joinability differs 6.5-fold, and the GNPS MGF export cannot be joined at all. All code, audit outputs and derivations are openly released.
Source: ChemRxiv
Authors: Oshoma Erumiseli, Bila Hassan Ali, Dauda Garba
Institutions: Veritas University, University of Abuja
Language: English
Subfield: Spectroscopy
Field: Chemistry
Domain: Physical Sciences
Open Access status: green
OpenAlex ID: W7221768789