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Applying Tandem Mass Spectral Libraries for Solving the Critical Assessment of Small Molecule Identification (CASMI) LC/MS Challenge 2012.

ABSTRACT: The "Critical Assessment of Small Molecule Identification" (CASMI) contest was aimed in testing strategies for small molecule identification that are currently available in the experimental and computational mass spectrometry community. We have applied tandem mass spectral library search to solve Category 2 of the CASMI Challenge 2012 (best identification for high resolution LC/MS data). More than 230,000 tandem mass spectra part of four well established libraries (MassBank, the collection of tandem mass spectra of the "NIST/NIH/EPA Mass Spectral Library 2012", METLIN, and the 'Wiley Registry of Tandem Mass Spectral Data, MSforID') were searched. The sample spectra acquired in positive ion mode were processed. Seven out of 12 challenges did not produce putative positive matches, simply because reference spectra were not available for the compounds searched. This suggests that to some extent the limited coverage of chemical space with high-quality reference spectra is still a problem encountered in tandem mass spectral library search. Solutions were submitted for five challenges. Three compounds were correctly identified (kanamycin A, benzyldiphenylphosphine oxide, and 1-isopropyl-5-methyl-1H-indole-2,3-dione). In the absence of any reference spectrum, a false positive identification was obtained for 1-aminoanthraquinone by matching the corresponding sample spectrum to the structurally related compounds N-phenylphthalimide and 2-aminoanthraquinone. Another false positive result was submitted for 1H-benz[g]indole; for the 1H-benz[g]indole-specific sample spectra provided, carbazole was listed as the best matching compound. In this case, the quality of the available 1H-benz[g]indole-specific reference spectra was found to hamper unequivocal identification.

SUBMITTER: Oberacher H

PROVIDER: S-EPMC3901269 | biostudies-literature | 2013 Apr

REPOSITORIES: biostudies-literature

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Applying Tandem Mass Spectral Libraries for Solving the Critical Assessment of Small Molecule Identification (CASMI) LC/MS Challenge 2012.

Oberacher Herbert H

Metabolites 20130426 2

The "Critical Assessment of Small Molecule Identification" (CASMI) contest was aimed in testing strategies for small molecule identification that are currently available in the experimental and computational mass spectrometry community. We have applied tandem mass spectral library search to solve Category 2 of the CASMI Challenge 2012 (best identification for high resolution LC/MS data). More than 230,000 tandem mass spectra part of four well established libraries (MassBank, the collection of ta ...[more]

PMID: 24957994

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Project description:Mass spectrometry (MS) is the state-of-the-art methodology for capturing the breadth and depth of the immunopeptidome across human leukocyte antigen (HLA) allotypes and cell types. The majority of studies in the immunopeptidomics field are discovery driven. Hence, data-dependent tandem MS (MS/MS) acquisition (DDA) is widely used, as it generates high-quality references of peptide fingerprints. However, DDA suffers from the stochastic selection of abundant ions that impairs sensitivity and reproducibility. In contrast, in data-independent acquisition (DIA), the systematic fragmentation and acquisition of all fragment ions within given isolation m/z windows yield a comprehensive map for a given sample. However, many DIA approaches commonly require generating comprehensive DDA-based spectrum libraries, which can become impractical for studying noncanonical and personalized neoantigens. Because the amount of HLA peptides eluted from biological samples such as small tissue biopsies is typically not sufficient for acquiring both meaningful DDA data necessary for generating comprehensive spectral libraries and DIA MS measurements, the implementation of DIA in the immunopeptidomics translational research domain has remained limited. We implemented a DIA immunopeptidomics workflow and assessed its sensitivity and accuracy by matching DIA data against libraries with growing complexity-from sample-specific libraries to libraries combining 2 to 40 different immunopeptidomics samples. Analyzing DIA immunopeptidomics data against a complex multi-HLA spectral library resulted in a two-fold increase in peptide identification compared with sample-specific library and in a three-fold increase compared with DDA measurements, yet with no detrimental effect on the specificity. Furthermore, we demonstrated the implementation of DIA for sensitive personalized neoantigen discovery through the analysis of DIA data with predicted MS/MS spectra of clinically relevant HLA ligands. We conclude that a comprehensive multi-HLA library for DIA approach in combination with MS/MS prediction is highly advantageous for clinical immunopeptidomics, especially when low amounts of biological samples are available.

Dataset Information

Applying Tandem Mass Spectral Libraries for Solving the Critical Assessment of Small Molecule Identification (CASMI) LC/MS Challenge 2012.

Publications

Applying Tandem Mass Spectral Libraries for Solving the Critical Assessment of Small Molecule Identification (CASMI) LC/MS Challenge 2012.

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