title: Discovering and validating between-subject variations in plasma lipids in healthy subjects.
abstract: Lipid levels are commonly used in clinical settings as disease biomarkers, and the advent of mass spectrometry-based (MS) lipidomics heralds the possibility of identifying additional lipids that can inform disease predispositions. However, the degree of natural variation for many lipids remains poorly understood, thus confounding downstream investigations on whether a specific intervention is driving observed lipid fluctuations. Here, we performed targeted mass spectrometry with multiple reaction monitoring across a comprehensive spectrum of 192 plasma lipids on eight subjects across three time-points separated by six hours and two standardized meals. A validation study to confirm the initial discoveries was performed in a further set of nine subjects, subject to the identical study design. Technical variation of the MS was assessed using duplicate measurements in the validation study, while biological variation was measured for lipid species with coefficients of variation <20%. We observed that eight lipid species from the phosphatidylethanolamine and phosphatidylcholine lipid classes were discovered and validated to vary consistently across the three time-points, where the within-subject variance can be up to 1.3-fold higher than between-subject variance. These findings highlight the importance of understanding the range of biological variation in plasma lipids as a precursor to their use in clinical biochemistry.
authors.affiliation: NUS Graduate School for Integrative Science and Engineering, National University of Singapore, Singapore.|Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.|Life Sciences Institute, National University of Singapore, Singapore.
authors.forename: Husna
authors.initials: H
authors.lastname: Begum
authors.affiliation: Saw Swee Hock School of Public Health, National University of Singapore, Singapore.
authors.forename: Bowen
authors.initials: B
authors.lastname: Li
authors.affiliation: Life Sciences Institute, National University of Singapore, Singapore.|State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, China.
authors.forename: Guanghou
authors.initials: G
authors.lastname: Shui
authors.affiliation: Life Sciences Institute, National University of Singapore, Singapore.
authors.forename: Amaury
authors.initials: A
authors.lastname: Cazenave-Gassiot
authors.affiliation: Cancer Science Institute of Singapore, National University of Singapore, Singapore.
authors.forename: Richie
authors.initials: R
authors.lastname: Soong
authors.affiliation: Saw Swee Hock School of Public Health, National University of Singapore, Singapore.
authors.forename: Rick Twee-Hee
authors.initials: RT
authors.lastname: Ong
authors.affiliation: Life Sciences Institute, National University of Singapore, Singapore.
authors.forename: Peter
authors.initials: P
authors.lastname: Little
authors.affiliation: NUS Graduate School for Integrative Science and Engineering, National University of Singapore, Singapore.|Life Sciences Institute, National University of Singapore, Singapore.|Saw Swee Hock School of Public Health, National University of Singapore, Singapore.|Genome Institute of Singapore, Agency for Science, Technology and Research, Singapore.|Department of Statistics and Applied Probability, National University of Singapore, Singapore.
authors.forename: Yik-Ying
authors.initials: YY
authors.lastname: Teo
authors.affiliation: NUS Graduate School for Integrative Science and Engineering, National University of Singapore, Singapore.|Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.|Life Sciences Institute, National University of Singapore, Singapore.|Department of Biological Sciences, National University of Singapore, Singapore.
authors.forename: Markus R
authors.initials: MR
authors.lastname: Wenk
mesh_terms: D000328:Adult; D002851:Chromatography, High Pressure Liquid; D005260:Female; D064368:Healthy Volunteers; D006801:Humans; D050356:Lipid Metabolism / Q000502:physiology*; D008297:Male; D013058:Mass Spectrometry; D015588:Observer Variation; D010713:Phosphatidylcholines / Q000097:blood*; D010714:Phosphatidylethanolamines / Q000097:blood*; D010865:Pilot Projects; D012016:Reference Values; D015203:Reproducibility of Results; D012846:Singapore
chemical_list: D010713:Phosphatidylcholines; D010714:Phosphatidylethanolamines; C483858:phosphatidylethanolamine