Renai Lapo, Ulaszewska Marynka, Mattivi Fulvio, Bartoletti Riccardo, Del Bubba Massimo, van der Hooft Justin J J
Department of Chemistry, University of Florence, Via della Lastruccia 3, Sesto Fiorentino, 50019 Florence, Italy.
Bioinformatics Group, Wageningen University, 6708 PB Wageningen, The Netherlands.
Metabolites. 2022 Oct 21;12(10):1005. doi: 10.3390/metabo12101005.
Untargeted metabolomics approaches deal with complex data hindering structural information for the comprehensive analysis of unknown metabolite features. We investigated the metabolite discovery capacity and the possible extension of the annotation coverage of the Feature-Based Molecular Networking (FBMN) approach by adding two novel nutritionally-relevant (contextual) mass spectral libraries to the existing public ones, as compared to widely-used open-source annotation protocols. Two contextual mass spectral libraries in positive and negative ionization mode of ~300 reference molecules relevant for plant-based nutrikinetic studies were created and made publicly available through the GNPS platform. The postprandial urinary metabolome analysis within the intervention of supplements was selected as a case study. Following the FBMN approach in combination with the added contextual mass spectral libraries, 67 berry-related and human endogenous metabolites were annotated, achieving a structural annotation coverage comparable to or higher than existing non-commercial annotation workflows. To further exploit the quantitative data obtained within the FBMN environment, the postprandial behavior of the annotated metabolites was analyzed with Pearson product-moment correlation. This simple chemometric tool linked several molecular families with phase II and phase I metabolism. The proposed approach is a powerful strategy to employ in longitudinal studies since it reduces the unknown chemical space by boosting the annotation power to characterize biochemically relevant metabolites in human biofluids.
非靶向代谢组学方法处理的复杂数据阻碍了对未知代谢物特征进行全面分析的结构信息。我们研究了基于特征的分子网络（FBMN）方法的代谢物发现能力以及注释覆盖范围的可能扩展，通过在现有的公共质谱库中添加两个与营养相关的新型（上下文）质谱库，并与广泛使用的开源注释协议进行比较。创建了两个与植物性营养动力学研究相关的约300种参考分子的正离子和负离子模式下的上下文质谱库，并通过GNPS平台公开提供。选择补充剂干预期间的餐后尿液代谢组分析作为案例研究。遵循FBMN方法并结合添加的上下文质谱库，注释了67种与浆果相关的和人类内源性代谢物，实现了与现有非商业注释工作流程相当或更高的结构注释覆盖范围。为了进一步利用在FBMN环境中获得的定量数据，用Pearson积矩相关性分析了注释代谢物的餐后行为。这个简单的化学计量工具将几个分子家族与II期和I期代谢联系起来。所提出的方法是纵向研究中一种强大的策略，因为它通过增强注释能力来减少未知化学空间，从而表征人类生物流体中与生物化学相关的代谢物。
