Plasma Instead of Serum Avoids Critical Confounding of Clinical Metabolomics Studies by Platelets
- Author(s)
- Gerhard Hagn, Samuel M. Meier-Menches, Günter Plessl-Walder, Gaurav Mitra, Thomas Mohr, Karin Preindl, Andreas Schlatter, Doreen Schmidl, Christopher Gerner, Gerhard Garhöfer, Andrea Bileck
- Abstract
Metabolomics is an emerging and powerful bioanalytical method supporting clinical investigations. Serum and plasma are commonly used without rational prioritization. Serum is collected after blood coagulation, a complex biochemical process involving active platelet metabolism. This may affect the metabolome and increase the variance, as platelet counts and function may vary substantially in individuals. A multiomics approach systematically investigating the suitability of serum and plasma for clinical studies demonstrated that metabolites correlated well (n = 461, R2 = 0.991), whereas lipid mediators (n = 83, R2 = 0.906) and proteins (n = 322, R2 = 0.860) differed substantially between specimen. Independently, analysis of platelet releasates identified most biomolecules significantly enriched in serum compared to plasma. A prospective, randomized, controlled parallel group metabolomics trial with acetylsalicylic acid administered for 7 days demonstrated that the apparent drug effects significantly differ depending on the analyzed specimen. Only serum analyses of healthy individuals suggested a significant downregulation of TXB2 and 12-HETE, which were specifically formed during coagulation in vitro. Plasma analyses reliably identified acetylsalicylic acid effects on metabolites and lipids occurring in vivo such as an increase in serotonin, 15-deoxy-PGJ2 and sphingosine-1-phosphate and a decrease in polyunsaturated fatty acids. The present data suggest that plasma should be preferred above serum for clinical metabolomics studies as the serum metabolome may be substantially confounded by platelets.
- Organisation(s)
- Department of Analytical Chemistry, Department of Inorganic Chemistry, Joint Metabolome Facility, Mass Spectrometry Centre
- External organisation(s)
- Vienna Doctoral School in Chemistry (DoSChem), Medizinische Universität Wien
- Journal
- Journal of Proteome Research
- Volume
- 23
- Pages
- 3064-3075
- No. of pages
- 12
- ISSN
- 1535-3893
- DOI
- https://doi.org/10.1021/acs.jproteome.3c00761
- Publication date
- 03-2024
- Peer reviewed
- Yes
- Austrian Fields of Science 2012
- 106037 Proteomics, 104002 Analytical chemistry
- Keywords
- ASJC Scopus subject areas
- General Chemistry, Biochemistry
- Portal url
- https://ucrisportal.univie.ac.at/en/publications/784c6879-ce6d-4245-8a39-01f30f1032be