Metabolomics biomarker

D. Kell. Metabolomic biomarkers search, discovery and validation. Expert Rev. Mol. Diagn., 7 329-333, 2007. 

Characterizing the metabolome is only one component which needs to be integrated with its counterparts to realize its potential contributions to drug discovery and development. When all of the work has been done to define the universe of the transcriptome, proteome, and metabolome, and biomarker sets have been identified, 90% of the work remains in the validation and acceptance of these patterns. 

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. 

Soga, T., Baran, R., Suematsu, M., Ueno, Y, Ikeda, S., Sakurakawa, T., Kakazu, Y, Ishikawa, T., Robert, M., Nishioka, T. and Tomita, M. (2006) Differential metabolomics reveals ophthalmic add as an oxidative stress biomarker indicating hepatic glutathione consumption. Joumol of Biological Chemistry, 281 (24), 16768-16776. 

Metabolomics analysis with the devTOX platform was performed in collaboration with Stemina Biomarker Discovery, Inc. 

Although Metabolomics is still in its infancy in AD investigation, a number of studies have been published in the last years (Table 1), as this chapter shows. Most of them are based on the analysis of CSF, blood, or postmortem BT samples, although in a lesser extent, urine has also been examined in the search of AD biomarkers (81,87). 

To date, the frame in the discovery phase, within the global biomarker finding process, is the common aspect of all metabolomic works linked to AD. Thus, most of metabolomic studies have been focused in the search of new biomarker candidates in the apparition and development of AD with high impact on novel hypotheses generation. Currently, there is a growing need to reliably validate those findings by increasing the cohort of clinical patients, to measure and validate the potential of the revealed biomarkers. 

Application of Metabolomics to Cardiovascular and Renal Disease Biomarker Discovery... 

FIGURE 1 Overview of metabolomics approaches in the discovery of cardiovascular and renal disease biomarkers. 

Yap et al. investigated a population of biomarkers that might relate the difference in CVD risk between southern and northern Chinese population by 1H NMR spectroscopy-based metabolome-wide association approach (21). The study was carried out among 4680 men and women ages 40-59 years from 17 diverse population samples in China, Japan, United Kingdom, and United... 

MICROVESICLES A NOVEL SOURCE OF BIOMARKERS 6.1 Metabolomics in Exosomes Research... 

MPs (also called microvesicles) are present in the blood of healthy individuals and are increased in various diseases including CVD. They are small membrane vesicles derived from activated and apoptotic cells. Importantly, MPs have been proposed to play roles in thrombosis, inflammation, and angiogenesis (103). MPs are also released in the circulation (104), and ever since their potent procoagulatory properties were first recognized in the field of homeostasis (105), the interest in their potential pathophysiological importance has increased (106). MP metabolome may be a useful and reliable source of biologically relevant disease biomarkers. 

In the immediate future, many other common problems of pregnancy and the fetus are likely to be reexamined by proteomics and metabolomics, ultimately identifying the best predictive biomarkers for disease and adverse neonatal outcome. As we have begun to see, pregnancy-induced hypertension (PIH), growth restriction in utero, diabetic pregnancy, and placental insufficiency are but a few of the situations in which early proteomic assessment is likely to play a prominent role in the next several years (Figure 8). 

Steroids hormones in clinical chemistry Comparison of RIA, GC-MS/MS and LC-MS/ MS in steroid analysis role of LC-MS/MS in metabolomics, e.g., quantitative bioanalysis, identifying and profiling biomarkers standardization of MS assavs. [14]... 

We will briefly highlight some examples using NMR methods [14, 19] but the remainder of this chapter will focus on MS and liquid chromatography-mass spectrometry (LC-MS) metabolomics [5, 15, 18]. We should also point out that there are a number of examples of both NMR and MS methods being used in the discovery of medicinally important biomarkers [23, 31] however, this review will focus more on the use of metabolomics to characterize proteins. 

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