Challenges and opportunities of metabolomics

Abstract

The metabolome is a data-rich source of information concerning all the low-molecular-weight metabolites in a biofluid, which can indicate early biological changes to the host due to perturbations in metabolic pathways. Major changes can be seen after minor stimuli, which make it a valuable target for analysis. Due to the diverse and sensitive nature of the metabolome, studies must be designed in a manner to maintain consistency, reduce variation between subjects, and optimize information recovery. Technological advancements in experimental design, mouse models and instrumentation have aided in this effort. Metabolomics has the ultimate potential to be valuable in a clinical setting where it could be used for early diagnosis of a disease and as a predictor of treatment response and survival. During drug treatment, the metabolic status of an individual could be monitored and used to indicate possible toxic effects. Metabolomics therefore has great potential for improving diagnosis, treatment and aftercare of disease.

Fig. 1.

Metabolomics contains the downstream products of genomic, transcriptomic, and proteomic processes.

Fig. 2.

GC X GC-TOFMS analysis of standard mixture showing (A) a three-dimensional surface plot of a selected region where metabolites elute at the same retention time on the primary column and can then be resolved by using a secondary column and (B) a contour plot of the same region showing separation of coeluting peaks

Fig. 3.

Identification ofurinary APAP metabolites by UPLC-MS-based metabolomics and stable-isotope tracing. A:PCA scores plot on 24 hurine samples from mice dosed with 400 mg/kg APAPΔ or 400 mg/kg [acetyl-²H₃] APAP▲. B: PCA loadings plot revealing ions in the urine samples after APAP and [acetyl-²H₃] APAP dosing.