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  4. Two-Dimensional Statistical Recoup ling for the Identification of Perturbed Metabolic Networks from NMR Spectroscopy
 
research article

Two-Dimensional Statistical Recoup ling for the Identification of Perturbed Metabolic Networks from NMR Spectroscopy

Blaise, Benjamin J.
•
Navratil, Vincent
•
Domange, Celine
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2010
JOURNAL OF PROTEOME RESEARCH

The development of Statistical Total Correlation Spectroscopy (STOCSY), a representation of the autocorrelation matrix of a spectral data set as a 2D pseudospectrum, has allowed more reliable assignment of one- and two-dimensional NMR spectra acquired from the complex mixtures that are usually used in metabolomics/metabonomics studies, thus, improving precise identification of candidate biomarkers contained in metabolic signatures computed by multivariate statistical analysis. However, the correlations obtained cannot always be interpreted in terms of connectivities between metabolites. In this study, we combine statistical recoupling of variables (SRV) and STOCSY to identify perturbed metabolite systems. The resulting Recoupled-STOCSY (R-STOCSY) method provides a 2D correlation landscape based on the SRV clusters representing physical, chemical, and biological entities. This enables the identification of correlations between distant clusters and extends the recoupling scheme of SRV, which was previously limited to the association of neighboring clusters. This allows the recovery of only meaningful correlations between metabolic signals and significantly enhances the interpretation of STOCSY. The method is validated through the measurement of the distances between the metabolites involved in these correlations, within the whole metabolic network, which shows that the average shortest path length is significantly shorter for the correlations detected in this new way compared to metabolite couples randomly selected from within the entire KEGG metabolic network. This enables the identification without any a priori knowledge of the perturbed metabolic network. The R-STOCSY completes the recoupling procedure between distant clusters, further reducing the high dimensionality of metabolomics/metabonomics data set and finally allows the identification of composite biomarkers, highlighting disruption of particular metabolic pathways within a global metabolic network. This allows the perturbed metabolic network to be extracted through NMR based metabolomics/metabonomics in an automated, and statistical manner.

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Type
research article
DOI
10.1021/pr1002615
Web of Science ID

WOS:000281443700018

Author(s)
Blaise, Benjamin J.
Navratil, Vincent
Domange, Celine
Shintu, Laetitia
Dumas, Marc-Emmanuel
Elena-Herrmann, Benedicte
Emsley, Lyndon  
Toulhoat, Pierre
Date Issued

2010

Publisher

AMER CHEMICAL SOC

Published in
JOURNAL OF PROTEOME RESEARCH
Volume

9

Issue

9

Start page

4513

End page

4520

Subjects

NMR

•

metabolic profiling

•

network

•

STOCSY

Editorial or Peer reviewed

REVIEWED

Written at

OTHER

EPFL units
LRM  
Available on Infoscience
January 8, 2015
Use this identifier to reference this record
https://infoscience.epfl.ch/handle/20.500.14299/110019
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