Discovering Regulated Metabolite Families in Untargeted Metabolomics Studies
Discovering Regulated Metabolite Families in Untargeted Metabolomics Studies
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DOI：
10.1021/acs.analchem.6b01569
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发表时间：
2016-08-16
影响因子：
7.4
通讯作者：
Balcke, Gerd Ulrich
中科院分区：
文献类型：
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作者：
Treutler, Hendrik;Tsugawa, Hiroshi;Balcke, Gerd Ulrich
代谢物的质谱鉴定构成了一个主要的瓶颈，这大大限制了生物医学或植物研究中代谢组学研究的通量。在这里，我们提出了一种新的方法来分析代谢组学数据从非靶向的，数据独立的LC-MS/MS测量。通过MS 1丰度和MS/MS谱的综合分析，实现了受调控代谢物家族的鉴定。这种方法提供了比较代谢组学的代谢调控的全局视图。我们在Web应用程序“MetFamily”中实现了我们的方法，该应用程序可在http：//msbi上免费获得。ipb-halle.de/MetFamily/. MetFamily提供了基于MS 1信号强度的模式与MS/MS水平上相应结构相似性之间的动态联系。基于“实测MS/MS光谱”的分层聚类分析，将结构相关代谢物注释为代谢物家族。与MS 1模式的主成分分析的联合检查（其中该注释保留在加载中）有助于在代谢物家族水平上解释比较代谢组学数据。作为概念的证明，我们以完全无人监督的方式从野生型番茄Solanum habrochaites LA 1777中鉴定出“两个毛状体特异性代谢物家族，并基于早期出版物和NMR验证了我们的发现
The identification of metabolites by mass spectrometry constitutes a major bottleneck which considerably limits the throughput of metabolomics studies in biomedical or plant research. Here, we present a novel approach to analyze metabolomics data from untargeted, data-independent LC-MS/MS measurements. By integrated analysis of MS1 abundances and MS/MS spectra, the identification of regulated metabolite families is achieved. This approach offers a global view on metabolic regulation in comparative metabolomics. We implemented our approach in the web application "MetFamily", which is freely available at http://msbi. ipb-halle.de/MetFamily/. MetFamily provides a dynamic link between the patterns based on MS1-signal intensity and the corresponding structural similarity at the MS/MS level. Structurally related metabolites are annotated as metabolite families based on a hierarchical cluster analysis of "measured MS/MS spectra. Joint examination with principal component analysis of MS1 patterns, where this annotation is preserved in the loadings, facilitates the interpretation of comparative metabolomics data at the level of metabolite families. As a proof of concept, we identified "two trichome-specific metabolite families from wild-type tomato Solanum habrochaites LA1777 in a fully unsupervised manner and validated our findings based on earlier publications and with NMR