The role of metabolites and metabolomics in clinically applicable biomarkers of disease.

in Archives of toxicology (2011), 85(1), 5-17

Metabolomics allows the simultaneous and relative quantification of thousands of different metabolites within a given sample using sensitive and specific methodologies such as gas or liquid chromatography ... [more ▼]

Metabolomics allows the simultaneous and relative quantification of thousands of different metabolites within a given sample using sensitive and specific methodologies such as gas or liquid chromatography coupled to mass spectrometry, typically in discovery phases of studies. Biomarkers are biological characteristics that are objectively measured and evaluated as indicators of normal biological processes, pathological processes or pharmacologic responses to a therapeutic intervention. Biomarkers are widely used in clinical practice for the diagnosis, assessment of severity and response to therapy in a number of clinical disease states. In human studies, metabolomics has been applied to define biomarkers related to prognosis or diagnosis of a disease or drug toxicity/efficacy and in doing so hopes to provide greater pathophysiological understanding of disease or therapeutic toxicity/efficacy. This review discusses the application of metabolomics in the discovery and subsequent application of biomarkers in the diagnosis and management of inborn errors of metabolism, cardiovascular disease and cancer. We critically appraise how novel biomarkers discovered through metabolomic analysis may be utilized in future clinical practice by addressing the following three fundamental questions: (1) Can the clinician measure them? (2) Do they add new information? (3) Do they help the clinician to manage patients? Although a number of novel biomarkers have been discovered through metabolomic studies of human diseases in the last decade, none have currently made the transition to routine use in clinical practice. Metabolites identified from these early studies will need to form the basis of larger, prospective, externally validated studies in clinical cohorts for their future use as biomarkers. At this stage, the absolute quantification of these biomarkers will need to be assessed epidemiologically, as will the ultimate deployment in the clinic via routine biochemistry, dip stick or similar rapid at- or near-patient care technologies. [less ▲]

Automated workflows for accurate mass-based putative metabolite identification in LC/MS-derived metabolomic datasets.

in Bioinformatics (2011), 27(8), 1108-12

MOTIVATION: The study of metabolites (metabolomics) is increasingly being applied to investigate microbial, plant, environmental and mammalian systems. One of the limiting factors is that of chemically ... [more ▼]

MOTIVATION: The study of metabolites (metabolomics) is increasingly being applied to investigate microbial, plant, environmental and mammalian systems. One of the limiting factors is that of chemically identifying metabolites from mass spectrometric signals present in complex datasets. RESULTS: Three workflows have been developed to allow for the rapid, automated and high-throughput annotation and putative metabolite identification of electrospray LC-MS-derived metabolomic datasets. The collection of workflows are defined as PUTMEDID_LCMS and perform feature annotation, matching of accurate m/z to the accurate mass of neutral molecules and associated molecular formula and matching of the molecular formulae to a reference file of metabolites. The software is independent of the instrument and data pre-processing applied. The number of false positives is reduced by eliminating the inaccurate matching of many artifact, isotope, multiply charged and complex adduct peaks through complex interrogation of experimental data. AVAILABILITY: The workflows, standard operating procedure and further information are publicly available at http://www.mcisb.org/resources/putmedid.html. CONTACT: warwick.dunn@manchester.ac.uk. [less ▲]