Journal ArticleDOI
XCMS: processing mass spectrometry data for metabolite profiling using nonlinear peak alignment, matching, and identification.
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TLDR
An LC/MS-based data analysis approach, XCMS, which incorporates novel nonlinear retention time alignment, matched filtration, peak detection, and peak matching, and is demonstrated using data sets from a previously reported enzyme knockout study and a large-scale study of plasma samples.Abstract:
Metabolite profiling in biomarker discovery, enzyme substrate assignment, drug activity/specificity determination, and basic metabolic research requires new data preprocessing approaches to correlate specific metabolites to their biological origin. Here we introduce an LC/MS-based data analysis approach, XCMS, which incorporates novel nonlinear retention time alignment, matched filtration, peak detection, and peak matching. Without using internal standards, the method dynamically identifies hundreds of endogenous metabolites for use as standards, calculating a nonlinear retention time correction profile for each sample. Following retention time correction, the relative metabolite ion intensities are directly compared to identify changes in specific endogenous metabolites, such as potential biomarkers. The software is demonstrated using data sets from a previously reported enzyme knockout study and a large-scale study of plasma samples. XCMS is freely available under an open-source license at http://metlin...read more
Citations
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Metabolomics analysis reveals large effects of gut microflora on mammalian blood metabolites
William R. Wikoff,Andrew T. Anfora,Jun Liu,Peter G. Schultz,Scott A. Lesley,Eric C. Peters,Gary Siuzdak +6 more
TL;DR: A broad, drug-like phase II metabolic response of the host to metabolites generated by the microbiome was observed, suggesting that the gut microflora has a direct impact on the drug metabolism capacity of theHost.
Journal ArticleDOI
Procedures for large-scale metabolic profiling of serum and plasma using gas chromatography and liquid chromatography coupled to mass spectrometry
Warwick B. Dunn,David Broadhurst,David Broadhurst,Paul Begley,Eva Zelena,Sue Francis-McIntyre,Nadine Anderson,Marie Brown,Joshau D Knowles,Antony Halsall,John N. Haselden,Andrew W. Nicholls,Ian D. Wilson,Douglas B. Kell,Royston Goodacre +14 more
TL;DR: The experimental workflow for long-term and large-scale metabolomic studies involving thousands of human samples with data acquired for multiple analytical batches over many months and years is described.
Journal ArticleDOI
Innovation: Metabolomics: the apogee of the omics trilogy
TL;DR: By performing global metabolite profiling, also known as untargeted metabolomics, new discoveries linking cellular pathways to biological mechanism are being revealed and are shaping the understanding of cell biology, physiology and medicine.
Journal ArticleDOI
The re-emergence of natural products for drug discovery in the genomics era
TL;DR: This work reviews strategies for natural product screening that harness the recent technical advances that have reduced technical barriers and assess the use of genomic and metabolomic approaches to augment traditional methods of studying natural products.
Journal ArticleDOI
Discovery and resupply of pharmacologically active plant-derived natural products: A review.
Atanas G. Atanasov,Birgit Waltenberger,Eva-Maria Pferschy-Wenzig,Thomas Linder,Christoph Wawrosch,Pavel Uhrin,Veronika Temml,Limei Wang,Stefan Schwaiger,Elke H. Heiss,Judith M. Rollinger,Judith M. Rollinger,Daniela Schuster,Johannes M. Breuss,Valery N. Bochkov,Marko D. Mihovilovic,Brigitte Kopp,Rudolf Bauer,Verena M. Dirsch,Hermann Stuppner +19 more
TL;DR: While the intrinsic complexity of natural product-based drug discovery necessitates highly integrated interdisciplinary approaches, the reviewed scientific developments, recent technological advances, and research trends clearly indicate that natural products will be among the most important sources of new drugs in the future.
References
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Journal ArticleDOI
Bioconductor: open software development for computational biology and bioinformatics
Robert Gentleman,Vincent J. Carey,Douglas M. Bates,Benjamin M. Bolstad,Marcel Dettling,Sandrine Dudoit,Byron Ellis,Laurent Gautier,Yongchao Ge,Jeff Gentry,Kurt Hornik,Torsten Hothorn,Wolfgang Huber,Stefano Maria Iacus,Rafael A. Irizarry,Friedrich Leisch,Cheng Li,Martin Maechler,A. J. Rossini,Günther Sawitzki,Colin A. Smith,Gordon K. Smyth,Luke Tierney,Jean Yang,Jianhua Zhang +24 more
TL;DR: Details of the aims and methods of Bioconductor, the collaborative creation of extensible software for computational biology and bioinformatics, and current challenges are described.
Journal ArticleDOI
Metabolite profiling for plant functional genomics.
Oliver Fiehn,Joachim Kopka,Peter Dörmann,Thomas Altmann,Richard N. Trethewey,Lothar Willmitzer +5 more
TL;DR: The use of metabolite profiling is described as a new tool for a comparative display of gene function and has the potential not only to provide deeper insight into complex regulatory processes but also to determine phenotype directly.
Journal ArticleDOI
Parametric time warping.
TL;DR: A parametric model is proposed for the warping function when aligning chromatograms, allowing alignment of batches of chromatogram based on warping functions for a limited number of calibration samples.
Journal ArticleDOI
Assignment of endogenous substrates to enzymes by global metabolite profiling.
Alan Saghatelian,Sunia A. Trauger,Elizabeth J. Want,Edward G. Hawkins,Gary Siuzdak,Benjamin F. Cravatt +5 more
TL;DR: A general strategy for identifying endogenous substrates of enzymes by untargeted liquid chromatography-mass spectrometry (LC-MS) analysis of tissue metabolomes from wild-type and enzyme-inactivated organisms is described to discover several brain lipids regulated by the mammalian enzyme fatty acid amide hydrolase in vivo.
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