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.

[1]  Oliver Fiehn,et al.  Metabolomic database annotations via query of elemental compositions: Mass accuracy is insufficient even at less than 1 ppm , 2006, BMC Bioinformatics.

[2]  Oliver Fiehn,et al.  Seven Golden Rules for heuristic filtering of molecular formulas obtained by accurate mass spectrometry , 2007, BMC Bioinformatics.

[3]  Tomás Pluskal,et al.  Metabolic profiling of the fission yeast S. pombe: quantification of compounds under different temperatures and genetic perturbation. , 2009, Molecular bioSystems.

[4]  Egon L. Willighagen,et al.  Elemental composition determination based on MSn , 2011, Bioinform..

[5]  Florian Rasche,et al.  Towards de novo identification of metabolites by analyzing tandem mass spectra , 2008, ECCB.

[6]  William DeMaio,et al.  Spectral accuracy of molecular ions in an LTQ/Orbitrap mass spectrometer and implications for elemental composition determination , 2009, Journal of the American Society for Mass Spectrometry.

[7]  Florian Rasche,et al.  Computing fragmentation trees from tandem mass spectrometry data. , 2011, Analytical chemistry.

[8]  Zsuzsanna Lipták,et al.  SIRIUS: decomposing isotope patterns for metabolite identification , 2008, Bioinform..

[9]  Egon L. Willighagen,et al.  The Chemistry Development Kit (CDK): An Open-Source Java Library for Chemo-and Bioinformatics , 2003, J. Chem. Inf. Comput. Sci..

[10]  A. Marshall,et al.  High-resolution mass spectrometers. , 2008, Annual review of analytical chemistry.

[11]  Matej Oresic,et al.  MZmine 2: Modular framework for processing, visualizing, and analyzing mass spectrometry-based molecular profile data , 2010, BMC Bioinformatics.

[12]  Ernö Pretsch,et al.  Structure Determination of Organic Compounds: Tables of Spectral Data , 2020 .

[13]  Chris F. Taylor,et al.  A common open representation of mass spectrometry data and its application to proteomics research , 2004, Nature Biotechnology.

[14]  Oliver Fiehn,et al.  Advances in structure elucidation of small molecules using mass spectrometry , 2010, Bioanalytical reviews.

[15]  J. Trottier,et al.  Book Review: Mass Spectrometry: Principles and Applications. E. de Hoffman, J. Charette and W. Stroobant. Wiley, Chichester 1996. ISBN 0 471 96697 5 , 1997 .

[16]  S. Kanaya,et al.  Summary , 1940, Intellectual Property in the Conflict of Laws.

[17]  Norbert Stoll,et al.  Isotope pattern evaluation for the reduction of elemental compositions assigned to high-resolution mass spectral data from electrospray ionization fourier transform ion cyclotron resonance mass spectrometry , 2006, Journal of the American Society for Mass Spectrometry.

[18]  A. Marshall,et al.  Scaling MS plateaus with high-resolution FT-ICRMS. , 2002, Analytical chemistry.

[19]  Yongdong Wang,et al.  The concept of spectral accuracy for MS. , 2010, Analytical chemistry.