Simulated-to-real benchmarking of acquisition methods in untargeted metabolomics

Wandy, J. , Mcbride, R., Rogers, S. , Terzis, N., Weidt, S., van der Hooft, J. J.J. , Bryson, K. , Daly, R. and Davies, V. (2023) Simulated-to-real benchmarking of acquisition methods in untargeted metabolomics. Frontiers in Molecular Biosciences, 10, 1130781. (doi: 10.3389/fmolb.2023.1130781) (PMID:36959982) (PMCID:PMC10027714)

[img] Text
292946.pdf - Published Version
Available under License Creative Commons Attribution.



Data-Dependent and Data-Independent Acquisition modes (DDA and DIA, respectively) are both widely used to acquire MS2 spectra in untargeted liquid chromatography tandem mass spectrometry (LC-MS/MS) metabolomics analyses. Despite their wide use, little work has been attempted to systematically compare their MS/MS spectral annotation performance in untargeted settings due to the lack of ground truth and the costs involved in running a large number of acquisitions. Here, we present a systematic in silico comparison of these two acquisition methods in untargeted metabolomics by extending our Virtual Metabolomics Mass Spectrometer (ViMMS) framework with a DIA module. Our results show that the performance of these methods varies with the average number of co-eluting ions as the most important factor. At low numbers, DIA outperforms DDA, but at higher numbers, DDA has an advantage as DIA can no longer deal with the large amount of overlapping ion chromatograms. Results from simulation were further validated on an actual mass spectrometer, demonstrating that using ViMMS we can draw conclusions from simulation that translate well into the real world. The versatility of the Virtual Metabolomics Mass Spectrometer (ViMMS) framework in simulating different parameters of both Data-Dependent and Data-Independent Acquisition (DDA and DIA) modes is a key advantage of this work. Researchers can easily explore and compare the performance of different acquisition methods within the ViMMS framework, without the need for expensive and time-consuming experiments with real experimental data. By identifying the strengths and limitations of each acquisition method, researchers can optimize their choice and obtain more accurate and robust results. Furthermore, the ability to simulate and validate results using the ViMMS framework can save significant time and resources, as it eliminates the need for numerous experiments. This work not only provides valuable insights into the performance of DDA and DIA, but it also opens the door for further advancements in LC-MS/MS data acquisition methods.

Item Type:Articles
Glasgow Author(s) Enlighten ID:McBride, Mr Ross and Weidt, Dr Stefan and Davies, Dr Vinny and Wandy, Dr Joe and Daly, Dr Ronan and Van Der Hooft, Mr Justin and Bryson, Dr Kevin and Rogers, Dr Simon
Authors: Wandy, J., Mcbride, R., Rogers, S., Terzis, N., Weidt, S., van der Hooft, J. J.J., Bryson, K., Daly, R., and Davies, V.
College/School:College of Medical Veterinary and Life Sciences > School of Infection & Immunity
College of Science and Engineering > School of Computing Science
College of Science and Engineering > School of Mathematics and Statistics > Statistics
Journal Name:Frontiers in Molecular Biosciences
Publisher:Frontiers Media
ISSN (Online):2296-889X
Copyright Holders:Copyright © 2023 Wandy, McBride, Rogers, Terzis, Weidt, van der Hooft, Bryson, Daly and Davies
First Published:First published in Frontiers in Molecular Biosciences 10: 1130781
Publisher Policy:Reproduced under a Creative Commons License
Data DOI:10.5525/gla.researchdata.1382

University Staff: Request a correction | Enlighten Editors: Update this record

Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
300982Exploiting Closed-Loop Aspects in Computationally and Data Intensive AnalyticsRoderick Murray-SmithEngineering and Physical Sciences Research Council (EPSRC)EP/R018634/1Computing Science