Quality control for building libraries from electrospray ionization tandem mass spectra.

Electrospray ionization (ESI) tandem mass spectrometry coupled with liquid chromatography is a routine technique for identifying and quantifying compounds in complex mixtures. The identification step can be aided by matching acquired tandem mass spectra (MS(2)) against reference library spectra as is routine for electron ionization (EI) spectra from gas chromatography/mass spectrometry (GC/MS). However, unlike the latter spectra, ESI MS(2) spectra are likely to originate from various precursor ions for a given target molecule and may be acquired at varying energies and resolutions and have characteristic noise signatures, requiring processing methods very different from EI to obtain complete and high quality reference spectra for individual analytes. This paper presents procedures developed for creating a tandem mass spectral library that addresses these factors. Library building begins by acquiring MS(2) spectra for all major MS(1) peaks in an infusion run, followed by assigning MS(2) spectra to clusters and creating a consensus spectrum for each. Intensity-based constraints for cluster membership were developed, as well as peak testing to recognize and eliminate suspect peaks and reduce noise. Consensus spectra were then examined by a human evaluator using a number of criteria, including a fraction of annotated peaks and consistency of spectra for a given ion at different energies. These methods have been developed and used to build a library from >9000 compounds, yielding 230,000 spectra.

[1]  Dmitrii V. Tchekhovskoi,et al.  The critical evaluation of a comprehensive mass spectral library , 1999, Journal of the American Society for Mass Spectrometry.

[2]  E. Go,et al.  Database Resources in Metabolomics: An Overview , 2010, Journal of Neuroimmune Pharmacology.

[3]  Jerry Zweigenbaum,et al.  Development and practical application of a library of CID accurate mass spectra of more than 2,500 toxic compounds for systematic toxicological analysis by LC–QTOF-MS with data-dependent acquisition , 2011, Analytical and bioanalytical chemistry.

[4]  Stephen E. Stein,et al.  Metabolite profiling of a NIST Standard Reference Material for human plasma (SRM 1950): GC-MS, LC-MS, NMR, and clinical laboratory analyses, libraries, and web-based resources. , 2013, Analytical chemistry.

[5]  W. Weinmann,et al.  ESI-MS/MS library of 1,253 compounds for application in forensic and clinical toxicology , 2009, Analytical and bioanalytical chemistry.

[6]  Y. Leblanc,et al.  Chemical noise reduction via mass spectrometry and ion/ion charge inversion: amino acids. , 2011, Analytical chemistry.

[7]  Dmitrii V. Tchekhovskoi,et al.  Developing qualitative LC-MS methods for characterization of Vaccinium berry Standard Reference Materials , 2013, Analytical and Bioanalytical Chemistry.

[8]  David S. Wishart,et al.  HMDB 3.0—The Human Metabolome Database in 2013 , 2012, Nucleic Acids Res..

[9]  S. Stein,et al.  Collisional energy dependence of peptide ion fragmentation , 2009, Journal of the American Society for Mass Spectrometry.

[10]  Ruedi Aebersold,et al.  Building consensus spectral libraries for peptide identification in proteomics , 2008, Nature Methods.

[11]  Nichole L. King,et al.  Development and validation of a spectral library searching method for peptide identification from MS/MS , 2007, Proteomics.

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

[13]  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.

[14]  Stephen Stein,et al.  Mass spectral reference libraries: an ever-expanding resource for chemical identification. , 2012, Analytical chemistry.

[15]  Stephen E. Stein,et al.  Chemical substructure identification by mass spectral library searching , 1995, Journal of the American Society for Mass Spectrometry.

[16]  Frank Suits,et al.  A noise model for mass spectrometry based proteomics , 2008, Bioinform..