Metabolomics: A Tool Ahead for Understanding Molecular Mechanisms of Drugs and Diseases (original) (raw)
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Metabolomics as a Challenging Approach for Medicinal Chemistry and Personalized Medicine
Journal of medicinal chemistry, 2016
"Omics" sciences have been developed to provide a holistic point of view of biology and to better understand the complexity of an organism as a whole. These systems biology approaches can be examined at different levels, starting from the most fundamental, i.e., the genome, and finishing with the most functional, i.e., the metabolome. Similar to how genomics is applied to the exploration of DNA, metabolomics is the qualitative and quantitative study of metabolites. This emerging field is clearly linked to genomics, transcriptomics and proteomics. In addition, metabolomics provides a unique and direct vision of the functional outcome of an organism's activities that are required for it to survive, grow and respond to internal and external stimuli or stress, e.g., pathologies and drugs. The links between metabolic changes, patient phenotype, physiological and/or pathological status and treatment are now well established and have opened a new area for the application of metabolomics in the drug discovery process and in personalized medicine.
Understanding Metabolomics in Biomedical Research
Endocrinology and metabolism (Seoul, Korea), 2015
The term "omics" refers to any type of specific study that provides collective information on a biological system. Representative omics includes genomics, proteomics, and metabolomics, and new omics is constantly being added, such as lipidomics or glycomics. Each omics technique is crucial to the understanding of various biological systems and complements the information provided by the other approaches. The main strengths of metabolomics are that metabolites are closely related to the phenotypes of living organisms and provide information on biochemical activities by reflecting the substrates and products of cellular metabolism. The transcriptome does not always correlate with the proteome, and the translated proteome might not be functionally active. Therefore, their changes do not always result in phenotypic alterations. Unlike the genome or proteome, the metabolome is often called the molecular phenotype of living organisms and is easily translated into biological cond...
Novel strategies for clinical investigation and biomarker discovery: a guide to applied metabolomics
Hormone Molecular Biology and Clinical Investigation, 2019
Metabolomics is an emerging technology that is increasing both in basic science and in human applications, providing a physiological snapshot. It has been highlighted as one of the most wide ranging and reliable tools for the investigation of physiological status, the discovery of new biomarkers and the analysis of metabolic pathways. Metabolomics uses innovative mass spectrometry (MS) allied to chromatography or nuclear magnetic resonance (NMR). The recent advances in bioinformatics, databases and statistics, have provided a unique perception of metabolites interaction and the dynamics of metabolic pathways at a system level. In this context, several studies have applied metabolomics in physiology-and disease-related works. The application of metabolomics includes, physiological and metabolic evaluation/monitoring, individual response to different exercise, nutritional interventions, pathological processes, responses to pharmacological interventions, biomarker discovery and monitoring for distinct aspects, such as: physiological capacity, fatigue/recovery and aging among other applications. For metabolomic analyses, despite huge improvements in the field, several complex methodological steps must be taken into consideration. In this regard, the present article aims to summarize the novel aspects of metabolomics and provide a guide for metabolomics for professionals related to physiologist and medical applications.
The Potential of Metabolomics in Biomedical Applications
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The metabolome offers a dynamic, comprehensive, and precise picture of the phenotype. Current high-throughput technologies have allowed the discovery of relevant metabolites that characterize a wide variety of human phenotypes with respect to health, disease, drug monitoring, and even aging. Metabolomics, parallel to genomics, has led to the discovery of biomarkers and has aided in the understanding of a diversity of molecular mechanisms, highlighting its application in precision medicine. This review focuses on the metabolomics that can be applied to improve human health, as well as its trends and impacts in metabolic and neurodegenerative diseases, cancer, longevity, the exposome, liquid biopsy development, and pharmacometabolomics. The identification of distinct metabolomic profiles will help in the discovery and improvement of clinical strategies to treat human disease. In the years to come, metabolomics will become a tool routinely applied to diagnose and monitor health and dis...
Metabolomics data and the biomarker qualification process
Metabolomics, 2012
Since its initial applications in healthcare research over a decade ago, metabolomics has matured into a technology that can now reliably detect and quantify hundreds of metabolites in biofluids and tissue samples. With substantial improvements in analytical capabilities in recent years, metabolomics now has the potential to provide sensitive and specific biomarkers of health and disease status, drug toxicity and therapeutic efficacy. Although many of the clinical biomarkers currently in use are metabolites such as glucose, cholesterol, and creatinine, few, if any, new metabolites (or panel of metabolites) derived from metabolomic analyses have been submitted to the FDA as biomarker candidates. Under a recent FDA draft Guidance for Industry from the Center for Drug Evaluation and Research (CDER), biomarkers discovered using metabolomics, like those derived from genetic, transcriptomic, and proteomic studies, may be submitted to CDER for consideration as new drug development tools and entered into a formal biomarker qualification process. The qualification process begins with a letter of intent from the submitter, followed by discussions with FDA and then the submission of data supporting the performance of the biomarker within a specific context of use. CDER forms a Biomarker Qualification Review Team at the start of the interactive process to advise the biomarker developer on the type of information important to support the proposed context of use, and review the data that evaluates the biomarker for the proposed context of use when the biomarker development appears complete and the full supporting data are submitted. Once qualified, a biomarker can be used in drug development within the qualified context of use without requesting additional regulatory review concerning its suitability.
Metabolomics in toxicology and preclinical research
ALTEX, 2013
Metabolomics, the comprehensive analysis of metabolites in a biological system, provides detailed information about the biochemical/physiological status of a biological system, and about the changes caused by chemicals. Metabolomics analysis is used in many fields, ranging from the analysis of the physiological status of genetically modified organisms in safety science to the evaluation of human health conditions. In toxicology, metabolomics is the -omics discipline that is most closely related to classical knowledge of disturbed biochemical pathways. It allows rapid identification of the potential targets of a hazardous compound. It can give information on target organs and often can help to improve our understanding regarding the mode-of-action of a given compound. Such insights aid the discovery of biomarkers that either indicate pathophysiological conditions or help the monitoring of the efficacy of drug therapies. The first toxicological applications of metabolomics were for me...
Herbs and Spices [Working Title], 2020
The aim of this chapter is to make a brief understanding on Metabolomics identification, extraction, and analysis techniques. As the name suggests, Metabolomics is the study of metabolites present in the body fluid (blood, plasma, urine, and saliva) or body parts (muscles, bone, tissue, and cells). These might be known metabolites or unknown metabolites. The metabolites can be endogenous (present in the body) or exogenous (formed by consuming external medicinal product). The molecular mass of these metabolites is usually lower (50-1500 Dalton) than the proteins and macromolecules. These metabolites can be extracted using various techniques such as solid phase extraction, liquid-liquid extraction, or simple protein precipitation. Extracted sample of metabolite then can be analyzed qualitatively or quantitatively using numerous analytical techniques such as high performance liquid chromatography (HPLC), liquid chromatography mass spectrometry (LC-MS/MS), dry blood spot (DBS), infrared (IR) spectroscopy, ultraviolet visible (UV) spectroscopy, nuclear magnetic resonance (NMR), ELISA, and chemiluminescence. Sensitivity of detection is the key factor, among many others, to decide which technique would be suitable for analysis. Liquid chromatography mass spectrometry (LC-MS/MS) is the latest and most sensitive technique among all the available methodology till date that has been extensively and exclusively used in current scenario.
Metabolomics enables precision medicine: "A White Paper, Community Perspective
Metabolomics : Official journal of the Metabolomic Society
Metabolomics 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 heal...