Highly Accurate Chemical Formula Prediction Tool Utilizing High-Resolution Mass Spectra, MS/MS Fragmentation, Heuristic Rules, and Isotope Pattern Matching

Mass spectrometry is commonly applied to qualitatively
and quantitatively
profile small molecules, such as peptides, metabolites, or lipids.
Modern mass spectrometers provide accurate measurements of mass-to-charge
ratios of ions, with errors as low as 1 ppm. Even such high mass accuracy,
however, is not sufficient to determine the unique chemical formula
of each ion, and additional algorithms are necessary. Here we present
a universal software tool for predicting chemical formulas from high-resolution
mass spectrometry data, developed within the MZmine 2 framework. The
tool is based on the use of a combination of heuristic techniques,
including MS/MS fragmentation analysis and isotope pattern matching.
The performance of the tool was evaluated using a real metabolomic
data set obtained with the Orbitrap MS detector. The true formula
was correctly determined as the highest-ranking candidate for 79%
of the tested compounds. The novel isotope pattern-scoring algorithm
outperformed a previously published method in 64% of the tested Orbitrap
spectra. The software described in this manuscript is freely available
and its source code can be accessed within the MZmine 2 source code
repository.