Augmentation of MS/MS Libraries with Spectral Interpolation for Improved Identification

Tandem mass spectrometry (MS/MS) is a primary tool for
the identification
of small molecules and metabolites where resultant spectra are most
commonly identified by matching them with spectra in MS/MS reference
libraries. The high degree of variability in MS/MS spectrum acquisition
techniques and parameters creates a significant challenge for building
standardized reference libraries. Here we present a method to improve
the usefulness of existing MS/MS libraries by augmenting available
experimental spectra data sets with statistically interpolated spectra
at unreported collision energies. We find that highly accurate spectral
approximations can be interpolated from as few as three experimental
spectra and that the interpolated spectra will be consistent with
true spectra gathered from the same instrument as the experimental
spectra. Supplementing existing spectral databases with interpolated
spectra yields consistent improvements to identification accuracy
on a range of instruments and precursor types. Applying this method
yields significant improvements (∼10% more spectra correctly
identified) on large data sets (2000–10 000 spectra),
indicating this is a quick yet adept tool for improving spectral matching
in situations where available reference libraries are not yet sufficient.
We also find improvements of matching spectra across instrument types
(between an Agilent Q-TOF and an Orbitrap Elite), at high collision
energies (50–90 eV), and with smaller data sets available through
MassBank.