A Systematic Evaluation of Blood Serum and Plasma Pre-Analytics for Metabolomics Cohort Studies

Abstract

The recent thriving development of biobanks and associated high-throughput phenotyping studies requires the elaboration of large-scale approaches for monitoring biological sample quality and compliance with standard protocols. We present a metabolomic investigation of human blood samples that delineates pitfalls and guidelines for the collection, storage and handling procedures for serum and plasma. A series of eight pre-processing technical parameters is systematically investigated along variable ranges commonly encountered across clinical studies. While metabolic fingerprints, as assessed by nuclear magnetic resonance, are not significantly affected by altered centrifugation parameters or delays between sample pre-processing (blood centrifugation) and storage, our metabolomic investigation highlights that both the delay and storage temperature between blood draw and centrifugation are the primary parameters impacting serum and plasma metabolic profiles. Storing the blood drawn at 4 °C is shown to be a reliable routine to confine variability associated with idle time prior to sample pre-processing. Based on their fine sensitivity to pre-analytical parameters and protocol variations, metabolic fingerprints could be exploited as valuable ways to determine compliance with standard procedures and quality assessment of blood samples within large multi-omic clinical and translational cohort studies.

Nutrimetabolomics: An Integrative Action for Metabolomic Analyses in Human Nutritional Studies

“…demonstrated that a high number of metabolites are significantly altered as a consequence of prolonged processing times at different temperatures, including signaling metabolites, lipids, carbohydrates, and amino acids. However, the most important changes can be associated with energy‐related metabolites (i.e., increased lactate, decreased glucose, and pyruvate), which could be attributable to the anaerobic metabolism of erythrocytes . Thus, as a general recommendation, blood processing times should be reduced to the minimum (preferably no longer than 2 h) and samples should be kept cool in the meantime.…”

A review of blood sample handling and pre‐processing for metabolomics studies

“…Hence, the sample handling is a relevant pre‐analytical factor significantly affecting the stability of the metabolome . Recently many studies examined several sample handling conditions relating to sample pre‐processing, storage and the variability of metabolite levels over time . That knowledge is required to estimate the reproducibility of metabolite measurements.…”

Reduced Glutamatergic Neurotransmission as Possible Indicator of Unfavorable Prognosis

“…This presents a great potential for their use in critical care medicine for understanding the relationships between the factors of microorganisms and the course of the pathological process that is key to improving the disease outcomes. [1] Metabolomics promotes the development of "personalized" medicine based on the application of patientspecific profiles, incorporating genetic and genomic data as well as clinical and environmental factors, to assess individual risks and to improve diagnostics and the target treatment. [2,3] GNS of humans and animals has a wide range of neurogenic and non-neurogenic functions, many of which are still little known.…”