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Journal article
Comprehensive Lipidomic Workflow for Multicohort Population Phenotyping Using Stable Isotope Dilution Targeted Liquid Chromatography-Mass Spectrometry
Journal of proteome research, Vol.22(5), pp.1419-1433
2023
PMID: 36828482
Abstract
Dysregulated lipid metabolism underpins many chronic diseases including cardiometabolic diseases. Mass spectrometry-based lipidomics is an important tool for understanding mechanisms of lipid dysfunction and is widely applied in epidemiology and clinical studies. With ever-increasing sample numbers, single batch acquisition is often unfeasible, requiring advanced methods that are accurate and robust to batch-to-batch and interday analytical variation. Herein, an optimized comprehensive targeted workflow for plasma and serum lipid quantification is presented, combining stable isotope internal standard dilution, automated sample preparation, and ultrahigh performance liquid chromatography-tandem mass spectrometry with rapid polarity switching to target 1163 lipid species spanning 20 subclasses. The resultant method is robust to common sources of analytical variation including blood collection tubes, hemolysis, freeze-thaw cycles, storage stability, analyte extraction technique, interinstrument variation, and batch-to-batch variation with 820 lipids reporting a relative standard deviation of <30% in 1048 replicate quality control plasma samples acquired across 16 independent batches (total injection count = 6142). However, sample hemolysis of ≥0.4% impacted lipid concentrations, specifically for phosphatidylethanolamines (PEs). Low interinstrument variability across two identical LC-MS systems indicated feasibility for intra/inter-lab parallelization of the assay. In summary, we have optimized a comprehensive lipidomic protocol to support rigorous analysis for large-scale, multibatch applications in precision medicine. The mass spectrometry lipidomics data have been deposited to massIVE: data set identifiers MSV000090952 and 10.25345/C5NP1WQ4S.
Details
- Title
- Comprehensive Lipidomic Workflow for Multicohort Population Phenotyping Using Stable Isotope Dilution Targeted Liquid Chromatography-Mass Spectrometry
- Authors/Creators
- Monique J Ryan - Murdoch University, Australian National Phenome CentreAlanah Grant-St James - Centre for Computational and Systems Medicine, Health Futures Institute, Harry Perkins Institute, Murdoch University, 5 Robin Warren Drive, Perth, Western Australia 6150, AustraliaNathan G Lawler - Murdoch University, Health Futures InstituteMark W Fear - The University of Western AustraliaEdward Raby - Pathwest Laboratory MedicineFiona M Wood - The University of Western AustraliaGarth L Maker - Murdoch University, Centre for Computational and Systems MedicineJulien Wist - Murdoch University, Centre for Computational and Systems MedicineElaine Holmes - Murdoch University, Centre for Computational and Systems MedicineJeremy K Nicholson - Murdoch University, Health Futures InstituteLuke Whiley - Murdoch University, Centre for Computational and Systems MedicineNicola Gray - Murdoch University, Centre for Computational and Systems Medicine
- Publication Details
- Journal of proteome research, Vol.22(5), pp.1419-1433
- Publisher
- American Chemical Society
- Identifiers
- 991005581070007891
- Copyright
- © 2023 The Authors.
- Murdoch Affiliation
- Australian National Phenome Centre; Centre for Computational and Systems Medicine
- Language
- English
- Resource Type
- Journal article
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- Collaboration types
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- Citation topics
- 2 Chemistry
- 2.211 Mass Spectrometry
- 2.211.990 Metabolomics
- Web Of Science research areas
- Biochemical Research Methods
- ESI research areas
- Biology & Biochemistry