Rochat Bertrand, Mohamed Rayane, Sottas Pierre-Edouard
Protein Analysis Facility, Center for Integrative Genomics (CIG), University of Lausanne, CH-1015 Lausanne, Switzerland.
Département Formation Recherche, Centre Hospitalier Universitaire Vaudois (CHUV), CH-1011 Lausanne, Switzerland.
Metabolites. 2018 Jun 15;8(2):39. doi: 10.3390/metabo8020039.
Today’s high-resolution mass spectrometers (HRMS) allow bioanalysts to perform untargeted/global determinations that can reveal unexpected compounds or concentrations in a patient’s sample. This could be performed for preliminary diagnosis attempts when usual diagnostic processes and targeted determinations fail. We have evaluated an untargeted diagnostic screening (UDS) procedure. UDS is a metabolome analysis that compares one sample (e.g., a patient) with control samples (a healthy population). Using liquid chromatography (LC)-HRMS full-scan analysis of human serum extracts and unsupervised data treatment, we have compared individual samples that were spiked with one xenobiotic or a higher level of one endogenous compound with control samples. After the use of different filters that drastically reduced the number of metabolites detected, the spiked compound was eventually revealed in each test sample and ranked. The proposed UDS procedure appears feasible and reliable to reveal unexpected xenobiotics (toxicology) or higher concentrations of endogenous metabolites. HRMS-based untargeted approaches could be useful as preliminary diagnostic screening when canonical processes do not reveal disease etiology nor establish a clear diagnosis and could reduce misdiagnosis. On the other hand, the risk of overdiagnosis of this approach should be reduced with mandatory biomedical interpretation of the patient’s UDS results and with confirmatory targeted and quantitative determinations.
如今的高分辨率质谱仪（HRMS）使生物分析人员能够进行非靶向/全局测定，从而揭示患者样本中意外的化合物或浓度。当常规诊断流程和靶向测定失败时，可进行此项操作以尝试初步诊断。我们评估了一种非靶向诊断筛查（UDS）程序。UDS是一种代谢组分析，可将一个样本（如患者样本）与对照样本（健康人群）进行比较。通过对人血清提取物进行液相色谱（LC）-HRMS全扫描分析以及无监督数据处理，我们将添加了一种外源性物质或一种内源性化合物更高水平的单个样本与对照样本进行了比较。在使用了大幅减少检测到的代谢物数量的不同过滤器后，最终在每个测试样本中发现并对添加的化合物进行了排序。所提出的UDS程序在揭示意外的外源性物质（毒理学）或更高浓度的内源性代谢物方面似乎是可行且可靠的。当传统流程无法揭示疾病病因或无法明确诊断时，基于HRMS的非靶向方法作为初步诊断筛查可能会有所帮助，并可减少误诊。另一方面，应通过对患者UDS结果进行强制性生物医学解读以及进行确证性靶向和定量测定来降低这种方法过度诊断的风险。
