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Open Access Green möglich sobald Postprint bei der ZB eingereicht worden ist.
Nontargeted modification-specific metabolomics study based on liquid chromatography high-resolution mass spectrometry.
Anal. Chem. 86, 9146-9153 (2014)
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 nontargeted modification-specific metabolomics, is reported. A key aspect of this strategy was the combination of in-source collision-induced dissociation liquid chromatographymass 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 unknowns in metabolomics projects. Nontargeted modification-specific metabolomics opens a new perspective in systems biology.
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Publikationstyp
Artikel: Journalartikel
Dokumenttyp
Wissenschaftlicher Artikel
Schlagwörter
Modification-specific Proteomics; Posttranslational Modifications; Human Urine; Metabolism; Cancer; Identification; Acetylation; Strategies; Enrichment; Diagnosis
ISSN (print) / ISBN
0003-2700
e-ISSN
1520-6882
Zeitschrift
Analytical Chemistry
Quellenangaben
Band: 86,
Heft: 18,
Seiten: 9146-9153
Verlag
American Chemical Society (ACS)
Verlagsort
Washington
Nichtpatentliteratur
Publikationen
Begutachtungsstatus
Peer reviewed