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.
摘要:
代谢组学是一种支持临床研究的新兴且强大的生物分析方法。通常使用血清和血浆而没有合理的优先次序。血液凝固后收集血清,涉及血小板活性代谢的复杂生化过程。这可能会影响代谢组并增加变异,血小板计数和功能在个体中可能有很大差异。多组学方法系统地调查血清和血浆的临床研究的适用性表明,代谢物相关良好(n=461,R2=0.991),而脂质介质(n=83,R2=0.906)和蛋白质(n=322,R2=0.860)在样本之间有很大差异。独立地,血小板释放物的分析发现,与血浆相比,血清中大多数生物分子显着富集。一个潜在的,随机化,使用乙酰水杨酸给药7天的对照平行组代谢组学试验表明,根据所分析的样本,药物的表观效应显著不同.只有健康个体的血清分析表明TXB2和12-HETE的显着下调,在体外凝血过程中特别形成。血浆分析可靠地确定了乙酰水杨酸对体内代谢产物和脂质的影响,例如5-羟色胺的增加,15-脱氧-PGJ2和鞘氨醇-1-磷酸和多不饱和脂肪酸的减少。目前的数据表明,在临床代谢组学研究中,血浆应优先于血清,因为血清代谢组可能基本上被血小板混淆。