Abstract
Blood is a rich biological sample routinely collected in clinical and epidemiological studies. With advancements in high throughput -omics technology, such as metabolomics, epidemiology can now delve more deeply and comprehensively into biological mechanisms involved in the etiology of diseases. However, the impact of the blood collection tube matrix of samples collected needs to be carefully considered to obtain meaningful biological interpretations and understand how the metabolite signatures are affected by different tube types. In the present study, we investigated whether the metabolic profile of blood collected as serum differed from samples collected as ACD plasma, citrate plasma, EDTA plasma, fluoride plasma, or heparin plasma. We identified and quantified 50 metabolites present in all samples utilizing nuclear magnetic resonance (NMR) spectroscopy. The heparin plasma tubes performed the closest to serum, with only three metabolites showing significant differences, followed by EDTA which significantly differed for five metabolites, and fluoride tubes which differed in eleven of the fifty metabolites. Most of these metabolite differences were due to higher levels of amino acids in serum compared to heparin plasma, EDTA plasma, and fluoride plasma. In contrast, metabolite measurements from ACD and citrate plasma differed significantly for approximately half of the metabolites assessed. These metabolite differences in ACD and citrate plasma were largely due to significant interfering peaks from the anticoagulants themselves. Blood is one of the most banked samples and thus mining and comparing samples between studies requires understanding how the metabolite signature is affected by the different media and different tube types.
Highlights
Classical epidemiological studies seek to identify risk factors to determine the presence or absence of disease and health in a population
The metabolites cis-aconitate and ascorbate were excluded from any further analysis as they were not present in all tube types (Supplementary Figure S2)
We found that acid citrate dextrose (ACD) plasma and citrate plasma were very different from serum, largely due to significant interfering peaks in the nuclear magnetic resonance (NMR) spectra which originate from the anticoagulants themselves
Summary
Classical epidemiological studies seek to identify risk factors to determine the presence or absence of disease and health in a population. Blood is a rich biological sample that is sensitive to the effects of health or disease, genetic variation, environment, nutrition, or the impact of toxicants and is obtained and commonly biobanked as serum and plasma in large repositories that collect, process, store, and distribute samples for future scientific investigations. PMI All of Us aims to understand how a person’s genetics, environment, and lifestyle can help to determine the best approach to prevent or treat disease by collecting genetic data, health data, and biological samples (including serum, EDTA plasma, citrate plasma, heparin plasma). Understanding whether and/or how the blood collection tube matrices (anticoagulants) affect measurement of the metabolome is critical to successfully merge epidemiology and metabolomics
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