Metabolomic database annotations via query of elemental compositions: Mass accuracy is insufficient even at less than 1 ppm
- Author(s): Kind, T
- Fiehn, O
- et al.
Published Web Locationhttp://www.biomedcentral.com/1471-2105/7/234
Background: Metabolomic studies are targeted at identifying and
quantifying all metabolites in a given biological context. Among the tools used
for metabolomic research, mass spectrometry is one of the most powerful tools.
However, metabolomics by mass spectrometry always reveals a high number of
unknown compounds which complicate in depth mechanistic or biochemical
understanding. In principle, mass spectrometry can be utilized within
strategies of de novo structure elucidation of small molecules, starting with
the computation of the elemental composition of an unknown metabolite using
accurate masses with errors < 5 ppm (parts per million). However even with
very high mass accuracy (< 1 ppm) many chemically possible formulae are
obtained in higher mass regions. In automatic routines an additional orthogonal
filter therefore needs to be applied in order to reduce the number of potential
elemental compositions. This report demonstrates the necessity of isotope
abundance information by mathematical confirmation of the concept. Results:
High mass accuracy (< 1 ppm) alone is not enough to exclude enough
candidates with complex elemental compositions (C, H, N, S, O, P, and
potentially F, Cl, Br and Si). Use of isotopic abundance patterns as a single
further constraint removes > 95% of false candidates. This orthogonal filter
can condense several thousand candidates down to only a small number of
molecular formulas. Example calculations for 10, 5, 3, 1 and 0.1 ppm mass
accuracy are given. Corresponding software scripts can be downloaded from
http:// fiehnlab. ucdavis. edu. A comparison of eight chemical databases
revealed that PubChem and the Dictionary of Natural Products can be recommended
for automatic queries using molecular formulae. Conclusion: More than 1.6
million molecular formulae in the range 0 - 500 Da were generated in an
exhaustive manner under strict observation of mathematical and chemical rules.
Assuming that ion species are fully resolved (either by chromatography or by
high resolution mass spectrometry), we conclude that a mass spectrometer
capable of 3 ppm mass accuracy and 2% error for isotopic abundance patterns
outperforms mass spectrometers with less than 1 ppm mass accuracy or even
hypothetical mass spectrometers with 0.1 ppm mass accuracy that do not include
isotope information in the calculation of molecular formulae.
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