Journal article
Gaussian Mixture Modeling Extensions for Improved False Discovery Rate Estimation in GC-MS Metabolomics
Journal of the American Society for Mass Spectrometry, Vol.34(6), pp.1096-1104
06/07/2023
DOI: 10.1021/jasms.3c00039
PMID: 37084380
Abstract
The ability to reliably identify small molecules (e.g., metabolites) is key toward driving scientific advancement in metabolomics. Gas chromatography-mass spectrometry (GC-MS) is an analytic method that may be applied to facilitate this process. The typical GC-MS identification workflow involves quantifying the similarity of an observed sample spectrum and other features (e.g., retention index) to that of several references, noting the compound of the best-matching reference spectrum as the identified metabolite. While a deluge of similarity metrics exist, none quantify the error rate of generated identifications, thereby presenting an unknown risk of false identification or discovery. To quantify this unknown risk, we propose a model-based framework for estimating the false discovery rate (FDR) among a set of identifications. Extending a traditional mixture modeling framework, our method incorporates both similarity score and experimental information in estimating the FDR. We apply these models to identification lists derived from across 548 samples of varying complexity and sample type (e.g., fungal species, standard mixtures, etc.), comparing their performance to that of the traditional Gaussian mixture model (GMM). Through simulation, we additionally assess the impact of reference library size on the accuracy of FDR estimates. In comparing the best performing model extensions to the GMM, our results indicate relative decreases in median absolute estimation error (MAE) ranging from 12% to 70%, based on comparisons of the median MAEs across all hit-lists. Results indicate that these relative performance improvements generally hold despite library size; however FDR estimation error typically worsens as the set of reference compounds diminishes.
Details
- Title: Subtitle
- Gaussian Mixture Modeling Extensions for Improved False Discovery Rate Estimation in GC-MS Metabolomics
- Creators
- Javier E. Flores - Pacific Northwest National LaboratoryLisa M. Bramer - Pacific Northwest National LaboratoryDavid J. Degnan - Pacific Northwest National LaboratoryVanessa L. Paurus - Environmental Molecular Sciences LaboratoryYuri E. Corilo - Environmental Molecular Sciences LaboratoryChaevien S. Clendinen - Environmental Molecular Sciences Laboratory
- Resource Type
- Journal article
- Publication Details
- Journal of the American Society for Mass Spectrometry, Vol.34(6), pp.1096-1104
- DOI
- 10.1021/jasms.3c00039
- PMID
- 37084380
- NLM abbreviation
- J Am Soc Mass Spectrom
- ISSN
- 1044-0305
- eISSN
- 1879-1123
- Publisher
- Amer Chemical Soc
- Number of pages
- 9
- Grant note
- DE-AC05-76RL01830 / Biological and Environmental Research program
- Language
- English
- Date published
- 06/07/2023
- Academic Unit
- Biostatistics
- Record Identifier
- 9985112968702771
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