Dataset Information

Comprehensive comparison of in silico MS/MS fragmentation tools of the CASMI contest: database boosting is needed to achieve 93% accuracy.

ABSTRACT: In mass spectrometry-based untargeted metabolomics, rarely more than 30% of the compounds are identified. Without the true identity of these molecules it is impossible to draw conclusions about the biological mechanisms, pathway relationships and provenance of compounds. The only way at present to address this discrepancy is to use in silico fragmentation software to identify unknown compounds by comparing and ranking theoretical MS/MS fragmentations from target structures to experimental tandem mass spectra (MS/MS). We compared the performance of four publicly available in silico fragmentation algorithms (MetFragCL, CFM-ID, MAGMa+ and MS-FINDER) that participated in the 2016 CASMI challenge. We found that optimizing the use of metadata, weighting factors and the manner of combining different tools eventually defined the ultimate outcomes of each method. We comprehensively analysed how outcomes of different tools could be combined and reached a final success rate of 93% for the training data, and 87% for the challenge data, using a combination of MAGMa+, CFM-ID and compound importance information along with MS/MS matching. Matching MS/MS spectra against the MS/MS libraries without using any in silico tool yielded 60% correct hits, showing that the use of in silico methods is still important.

SUBMITTER: Blazenovic I

PROVIDER: S-EPMC5445034 | biostudies-literature | 2017 May

REPOSITORIES: biostudies-literature

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Comprehensive comparison of in silico MS/MS fragmentation tools of the CASMI contest: database boosting is needed to achieve 93% accuracy.

Blaženović Ivana I Kind Tobias T Torbašinović Hrvoje H Obrenović Slobodan S Mehta Sajjan S SS Tsugawa Hiroshi H Wermuth Tobias T Schauer Nicolas N Jahn Martina M Biedendieck Rebekka R Jahn Dieter D Fiehn Oliver O

Journal of cheminformatics 20170525 1

In mass spectrometry-based untargeted metabolomics, rarely more than 30% of the compounds are identified. Without the true identity of these molecules it is impossible to draw conclusions about the biological mechanisms, pathway relationships and provenance of compounds. The only way at present to address this discrepancy is to use in silico fragmentation software to identify unknown compounds by comparing and ranking theoretical MS/MS fragmentations from target structures to experimental tandem ...[more]

PMID: 29086039

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Project description:Compound identification from accurate mass MS/MS spectra is a bottleneck for untargeted metabolomics. In this study, we propose nine rules of hydrogen rearrangement (HR) during bond cleavages in low-energy collision-induced dissociation (CID). These rules are based on the classic even-electron rule and cover heteroatoms and multistage fragmentation. We evaluated our HR rules by the statistics of MassBank MS/MS spectra in addition to enthalpy calculations, yielding three levels of computational MS/MS annotation: "resolved" (regular HR behavior following HR rules), "semiresolved" (irregular HR behavior), and "formula-assigned" (lacking structure assignment). With this nomenclature, 78.4% of a total of 18506 MS/MS fragment ions in the MassBank database and 84.8% of a total of 36370 MS/MS fragment ions in the GNPS database were (semi-) resolved by predicted bond cleavages. We also introduce the MS-FINDER software for structure elucidation. Molecular formulas of precursor ions are determined from accurate mass, isotope ratio, and product ion information. All isomer structures of the predicted formula are retrieved from metabolome databases, and MS/MS fragmentations are predicted in silico. The structures are ranked by a combined weighting score considering bond dissociation energies, mass accuracies, fragment linkages, and, most importantly, nine HR rules. The program was validated by its ability to correctly calculate molecular formulas with 98.0% accuracy for 5063 MassBank MS/MS records and to yield the correct structural isomer with 82.1% accuracy within the top-3 candidates. In a test with 936 manually identified spectra from an untargeted HILIC-QTOF MS data set of human plasma, formulas were correctly predicted in 90.4% of the cases, and the correct isomer structure was retrieved at 80.4% probability within the top-3 candidates, including for compounds that were absent in mass spectral libraries. The MS-FINDER software is freely available at http://prime.psc.riken.jp/ .

Project description:BackgroundSmall-area estimation models are regularly commissioned by public health bodies to identify areas of greater inequality and target areas for intervention in a range of behaviours and outcomes. Such local modelling has not been completed for diet consumption in England despite diet being an important predictor of health status. The study sets out whether aspects of adult diet can be modelled from previously collected data to define and evaluate area-level interventions to address obesity and ill-health.MethodsAdults aged 16 years and over living in England. Consumption of fruit, vegetables, and sugar-sweetened beverages (SSB) are modelled using small-area estimation methods in English neighbourhoods (Middle Super Output Areas [MSOA]) to identify areas where reported portions are significantly different from recommended levels of consumption. The selected aspects of diet are modelled from respondents in the National Diet and Nutrition Survey using pooled data from 2008-2016.ResultsEstimates indicate that the average prevalence of adults consuming less than one portion of fruit, vegetables or 100% juice each day by MSOA is 6.9% (range of 4.3 to 14.7%, SE 0.06) and the average prevalence of drinking more than 330ml/day of SSB is 11.5% (range of 5.7 to 30.5%, SE 0.03). Credible intervals around the estimates are wider for SSB consumption. The results identify areas including regions in London, urban areas in the North of England and the South coast which may be prioritised for targeted interventions to support reduced consumption of SSB and/or an increase in portions of fruit and vegetables.ConclusionThese estimates provide valuable information at a finer spatial scale than is presently feasible, allowing for within-country and locality prioritisation of resources to improve diet. Local, targeted interventions to improve fruit and vegetable consumption such as subsidies or voucher schemes should be considered where consumption of these foods is predicted to be low.

Dataset Information

Comprehensive comparison of in silico MS/MS fragmentation tools of the CASMI contest: database boosting is needed to achieve 93% accuracy.

Publications

Comprehensive comparison of in silico MS/MS fragmentation tools of the CASMI contest: database boosting is needed to achieve 93% accuracy.

Similar Datasets

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