Department of Forensic Genetics and Forensic Toxicology, National Board of Forensic Medicine, 587 58 Linköping, Sweden.
RTI International, Research Triangle Park, North Carolina 27709, United States.
Chem Res Toxicol. 2021 Jun 21;34(6):1496-1502. doi: 10.1021/acs.chemrestox.0c00448. Epub 2021 Apr 23.
Metabolomics can be defined as the scientific field aiming at characterizing all low-weight molecules (so-called metabolites) in a biological system. At the time of death, the level and type of metabolites present will most likely reflect the events leading up to death.In this proof of concept study, we investigated the potential of post-mortem metabolomics by identifying post-mortem biomarkers, correlated these identified biomarkers with those reported in clinical metabolomics studies, and finally validated the models predictability of unknown autopsy cases. In this post-mortem metabolomics setting, ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry data from 404 post-mortem samples, including pneumonia cases and control cases, were processed using XCMS (R). Potential biomarkers were evaluated using principal component analysis and orthogonal partial least squares-discriminant analysis. Biomarkers were putatively annotated using an in-house database and the online databases METLIN and HMDB. The results showed that clear group separation was observed between pneumonia cases and control cases. The metabolites responsible for group separation belonged to a broad set of biological classes, such as amino acids, carnitines, lipids, nicotinamides, nucleotides, and steroids. Many of these metabolites have been reported as important in clinical manifestation of pneumonia. For the unknown autopsy cases, the sensitivity and specificity were 86 and 84%, respectively. This study successfully investigated the robustness and usability of post-mortem metabolomics in death investigations. The identified post-mortem biomarkers correlated well with biomarkers reported and identified through clinical research.
代谢组学可以被定义为旨在描述生物系统中所有低分子量分子（即代谢物）的科学领域。在死亡时，存在的代谢物的水平和类型很可能反映导致死亡的事件。在本概念验证研究中，我们通过鉴定死后生物标志物来研究死后代谢组学的潜力，将这些鉴定出的生物标志物与临床代谢组学研究中报告的生物标志物进行关联，最后验证模型对未知尸检案例的预测能力。在这个死后代谢组学环境中，使用 XCMS（R）处理了来自 404 个死后样本的超高效液相色谱-四极杆飞行时间质谱数据，包括肺炎病例和对照病例。使用主成分分析和正交偏最小二乘判别分析评估潜在的生物标志物。使用内部数据库和在线数据库 METLIN 和 HMDB 对生物标志物进行推测注释。结果表明，肺炎病例和对照病例之间观察到明显的分组分离。负责分组分离的代谢物属于广泛的生物类别，如氨基酸、肉碱、脂质、烟酰胺、核苷酸和类固醇。其中许多代谢物已被报道在肺炎的临床表现中很重要。对于未知的尸检案例，敏感性和特异性分别为 86%和 84%。这项研究成功地调查了死后代谢组学在死亡调查中的稳健性和可用性。鉴定出的死后生物标志物与通过临床研究报告和鉴定出的生物标志物密切相关。
