Metabolomics enables precision medicine: “A White Paper, Community Perspective”

Abstract

Introduction: Background to metabolomicsMetabolomics is the comprehensive study of the metabolome, the repertoire of biochemicals (or small molecules) present in cells, tissues, and body fluids. The study of metabolism at the global or “-omics” level is a rapidly growing field that has the potential to have a profound impact upon medical practice. At the center of metabolomics, is the concept that a person’s metabolic state provides a close representation of that individual’s overall health status. This metabolic state reflects what has been encoded by the genome, and modified by diet, environmental factors, and the gut microbiome. The metabolic profile provides a quantifiable readout of biochemical state from normal physiology to diverse pathophysiologies in a manner that is often not obvious from gene expression analyses. Today, clinicians capture only a very small part of the information contained in the metabolome, as they routinely measure only a narrow set of blood chemistry analytes to assess health and disease states. Examples include measuring glucose to monitor diabetes, measuring cholesterol and high density lipoprotein/low density lipoprotein ratio to assess cardiovascular health, BUN and creatinine for renal disorders, and measuring a panel of metabolites to diagnose potential inborn errors of metabolism in neonates.Objectives of White Paper—expected treatment outcomes and metabolomics enabling tool for precision medicineWe anticipate that the narrow range of chemical analyses in current use by the medical community today will be replaced in the future by analyses that reveal a far more comprehensive metabolic signature. This signature is expected to describe global biochemical aberrations that reflect patterns of variance in states of wellness, more accurately describe specific diseases and their progression, and greatly aid in differential diagnosis. Such future metabolic signatures will: (1) provide predictive, prognostic, diagnostic, and surrogate markers of diverse disease states; (2) inform on underlying molecular mechanisms of diseases; (3) allow for sub-classification of diseases, and stratification of patients based on metabolic pathways impacted; (4) reveal biomarkers for drug response phenotypes, providing an effective means to predict variation in a subject’s response to treatment (pharmacometabolomics); (5) define a metabotype for each specific genotype, offering a functional read-out for genetic variants: (6) provide a means to monitor response and recurrence of diseases, such as cancers: (7) describe the molecular landscape in human performance applications and extreme environments. Importantly, sophisticated metabolomic analytical platforms and informatics tools have recently been developed that make it possible to measure thousands of metabolites in blood, other body fluids, and tissues. Such tools also enable more robust analysis of response to treatment. New insights have been gained about mechanisms of diseases, including neuropsychiatric disorders, cardiovascular disease, cancers...

Reconciling evidence-based medicine and precision medicine in the era of big data: challenges and opportunities

“…This has allowed us, for instance, to sequence the genomes of hundreds of thousands of individuals, to determine the allele-specific compositions and relative abundances of RNA transcripts in numerous cell types and conditions, to explore protein [10] or metabolite [11] profiles, to reconstitute molecular, cellular or physiological mechanisms, pathways and networks, and thus to generate new testable scientific hypotheses.…”

Stability of targeted metabolite profiles of urine samples under different storage conditions

“…The field of metabolomics has garnered much attention in recent years (Beger et al 2016; Bouatra et al 2013). Potential biomarkers for diseases such as type 2 diabetes and metabolite signatures of medication use and lifestyle choices (e.g.…”

Considerations when choosing a genetic model organism for metabolomics studies

“…Metabolomics is an essential component of systems biology and is at the forefront of precision medicine [1]. The process by which genetic information (DNA) is transmitted into a measureable phenotype ( e.g .…”

“…disease) works through a cascade of physiological levels, each of which affects the ultimate phenotype (Figure 1). Like all physiological levels, the metabolome is highly influenced by genetic, environmental, and genotype-by-environment interactions [2–5]; however, the proximity of the metabolome to the ultimate phenotype makes it an especially good measure of an organism's physiology [1]. Metabolomics is still in its early stages and has many unsolved challenges, such as chemically identifying metabolites [6].…”