A strategy for modelling dynamic responses in metabolic samples characterized by GC/MS

A multivariate strategy for studying the metabolic response over time in urinary GC/MS data is presented and exemplified by a study of drug-induced liver toxicity in the rat. The strategy includes the generation of representative data through hierarchical multivariate curve resolution (H-MCR), highlighting the importance of obtaining resolved metabolite profiles for quantification and identification of exogenous (drug related) and endogenous compounds (potential biomarkers) and for allowing reliable comparisons of multiple samples through multivariate projections. Batch modelling was used to monitor and characterize the normal (control) metabolic variation over time as well as to map the dynamic response of the drug treated animals in relation to the control. In this way treatment related metabolic responses over time could be detected and classified as being drug related or being potential biomarkers. In summary the proposed strategy uses the relatively high sensitivity and reproducibility of GC/MS in combination with efficient multivariate curve resolution and data analysis to discover individual markers of drug metabolism and drug toxicity. The presented results imply that the strategy can be of great value in drug toxicity studies for classifying metabolic markers in relation to their dynamic responses as well as for biomarker identification.

NATURVETENSKAP Biologi hsv//swe
NATURAL SCIENCES Biological Sciences hsv//eng
GC/MS - metabolomics - metabonomics - batch modelling - toxicology - hepatotoxicity - curve resolution - chemometrics

Stenlund, HansUmeå universitet,Kemiska institutionen(Swepub:umu)hasstd97 (författare)
Moritz, ThomasUmeå universitet,Umeå Plant Science Centre (UPSC) (författare)
Trygg, JohanUmeå universitet,Kemiska institutionen,Computational Life Science Cluster (CLiC)(Swepub:umu)jotr0001 (författare)
Sjöström, MichaelUmeå universitet,Kemiska institutionen(Swepub:umu)misj0001 (författare)
Verheij, Elwin R (författare)
Lindberg, Johan (författare)
Schuppe-Koistinen, Ina (författare)
Antti, HenrikUmeå universitet,Kemiska institutionen(Swepub:umu)hean0004 (författare)
Umeå universitetKemiska institutionen (creator_code:org_t)

Ingår i:Metabolomics: Springer Science and Business Media LLC2:3, s. 135-1431573-38821573-3890

Av författaren/redakt...: Jonsson, Pär; Stenlund, Hans; Moritz, Thomas; Trygg, Johan; Sjöström, Michae ...; Verheij, Elwin R; visa fler...; Lindberg, Johan; Schuppe-Koistine ...; Antti, Henrik; visa färre...

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