Metabolomics conductance

All MS technologies require the establishment of method-specific mass libraries so that compounds in the spectra can be identified [212], a tedious task that has been restricted to large laboratories. Nevertheless, some of these efforts are driven by the metabolomics community, thereby requiring some sort of standardization to conduct comparable experiments, as has been proposed with the ArMet standard [216], Last but not the least, metabolomics experiments generate large amounts of data that need sophisticated analysis methods to extract biological information, usually based on multidimensional statistics [3, 5, 58, 209, 217, 218]. Metabolomics experiments as the basis for an analysis of the possible dynamics of metabolic networks are discussed in Section VIII. 

In vivo, measuring bile acids in plasma and urine should be revived as potential biomarkers in the modern metabolomic era. Then the first-order scientific question will become whether early and time-controlled fasting-level measurement of bile acid concentration in plasma and urine can become a sensitive and specific biomarker for drug-induced cholestasis and ultimately liver injury at later time-points [117] Clinical trials should be conducted to evaluate whether such bile acid measurements can be used as part of a predictive panel to identify patients who are at increased risk of drug-induced cholestasis. 

Metabolomics has made remarkable inroads into the environmental research community. Here, a major emphasis is to understand the impact that environmental stress, such as pollution and climate change, has on wildlife. Indeed, many government organizations monitor the prevalence of pollutants in certain species of wildlife as indicators of the exposure risk within the environment. Studies of Japanese medaka have been conducted to investigate the effects of trichloroethylene, a common environmental pollutant, and the pesticide dinoseb, on the development of fish embryos (44, 45). Similarly, cadmium toxicity has been examined in the bank vole and rat and has revealed changes in lipid metabolism that preceded classical nephrotoxicity (46, 47). Another study investigated the effects of environmental toxins on earthworms (48). In particular, the analysis of earthworm tissue extracts by NMR spectroscopy identified maltose as a potential biomarker for ecotoxicity within a metal-contaminated site. 

Increasing number of papers using combinations of different Omics approaches are published, whereas transcriptomics and metabolomics are often preferred. Combined analysis of both can be carried in different ways, as shown above. Different software tools have been developed for analysis of each single technology, but solutions for combined analysis are emerging. This is especially true for overrepresentation or enrichment analysis in high-level data fusion. With more powerful computer infrastructure available even low-level data fusion (e.g., correlation analysis) will be conducted. Here computational power will be needed because calculation time increases not linearly with data size but rather quadratic or higher. 

Unlike other omics techniques, it is clear that metabonomics is very much an emerging field and new lessons on how to conduct a proper metabonomics study are learned each day. A very positive development is that in an effort to standardize the reporting standards for metabonomics studies, a first draft of a minimum requirement for the description of the biological materials and/or processes examined in a metabolomic study involving mammalian subjects was published in 2007 [89],... 

A monse popnlation-based approach may also be employed to inform the mode of action for dmg toxicity. A recent demonstration of this apphcation is a stndy that ntilized a panel of inbred strains to investigate the molecnlar mechanisms of genetic sensitivity to isoniazid-induced steatosis (Church et al., 2014). The study was conducted as a consortia effort by manbers of the Health and Environmental Sciences Institute (HESl) s Apphcation of Genomics to Mechanism-based Risk Assessment Technical Committee. In that study, a combined transcriptontic, metabolomic, and pharmacoge-netic analysis was utilized to provide evidence for a novel hypothesis that isoniazid increases the capacity for formation of lipid droplets while concurrently reducing the capacity for exporting stored fat from the hepatocytes in sensitive strains. 

Generally, the applications in food metabolomics reported in the literature are conducted using reverse-phase LC. However, the combination of hydrophilic interaction chromatography (HILIC) gives the possibility of a better separation of polar compounds, extending food metabolic information. 

Probe electrospray ionization (PESI) and TOF-MS were used for direct profiling of phytochemicals in different parts of a fresh tulip bulb [80], which emphasized the possibility of conducting in-vivo MS analysis of less sensitive biological matrices such as plant tissues. Recently, Pan et al. [81] demonstrated single-probe MS which can conduct metabolomic analysis of individual living cells in real time. The diameter of this probe is < 10 pm which makes the device compatible with eukaryotic cells. Atmospheric pressure ion sources are particularly suitable for analysis of live biological specimens. Cellular metabolism does not need to be quenched before analysis. For instance, in laser ablation electrospray ionization (LAESI)-MS, cells are irradiated by a laser beam in order to extract small amounts of cytosolic components, and to transfer them to the ESI plume [82]. 

---