Nontargeted Modification-Specific Metabolomics Study Based on Liquid Chromatography鈥揌igh-Resolution Mass Spectrometry

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• 作者：Weidong Dai ; Peiyuan Yin ; Zhongda Zeng ; Hongwei Kong ; Hongwei Tong ; Zhiliang Xu ; Xin Lu ; Rainer Lehmann ; Guowang Xu
• 刊名：Analytical Chemistry
• 出版年：2014
• 出版时间：September 16, 2014
• 年：2014
• 卷：86
• 期：18
• 页码：9146-9153
• 全文大小：433K
• ISSN：1520-6882

文摘

Modifications of genes and proteins have been extensively studied in systems biology using comprehensive analytical strategies. Although metabolites are frequently modified, these modifications have not been studied using -omics approaches. Here a general strategy for the nontargeted profiling of modified metabolites, which we call 鈥渘ontargeted modification-specific metabolomics鈥? is reported. A key aspect of this strategy was the combination of in-source collision-induced dissociation liquid chromatography鈥搈ass spectrometry (LC-MS) and global nontargeted LC-MS-based metabolomics. Characteristic neutral loss fragments that are specific for acetylation, sulfation, glucuronidation, glucosidation, or ribose conjugation were reproducibly detected using human urine as a model specimen for method development. The practical application of this method was demonstrated by profiling urine samples from liver cirrhosis patients. Approximately 900 features were identified as modified endogenous metabolites and xenobiotics. Moreover, this strategy supports the identification of compounds not included in traditional metabolomics databases (HMDB, Metlin, and KEGG), which are currently referred to as 鈥渦nknowns鈥?in metabolomics projects. Nontargeted modification-specific metabolomics opens a new perspective in systems biology.