Metabolomics - a new era in bio(pharmaceutical) analysis
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The major aim of metabolomics is to identify and quantify all endogenous and exogenous small molecule metabolites in a biological system in a high-throughput manner. Metabolomics has the potential to deliver diagnostic biomarkers for the detection and prognosis of diseases, and the prediction of the efficacy and safety of pharmaceutical treatment. Metabolomics can also provide insights into the biochemical mechanisms of diseases and their modulation by drugs. The analytical platforms include NMR spectroscopy, masspectrometry combined with gas or liquid chromatography. Due to the complexity of the metabolome, no single analytical platform can be applied to detect all metabolites in a biological sample.Different conceptual approaches are used in metabolomics. Targeted (specific) metabolomics is a quantitative approach where a set of known metabolites are quantitated. The identities of metabolites were initially established based on the available databases and using standard compounds; the identified metabolite peaks are then quantified based on internal or external reference compounds. Targeted metabolomics can provide greater insights into the dynamics and fluxes of metabolites. Non-targeted (global) metabolomics aims for a quick and reliable identification of small molecule biomarkers characteristic for a particular physiological state in response to internal or external stimuli. This approach is often used in pharmacokinetic studies of drug metabolism and when looking at the effect of therapeutics or genetic modifications on a specific enzyme.The development of personalised metabolomics in the future, will give the opportunity to track the trends of the metabolome for personalised drugs and improved treatment strategies.Keywords:
Metabolome
Identification
Drug Development
Untargeted metabolomics is a promising approach for reducing the significant attrition rate for discovering and developing drugs in the pharmaceutical industry. This review aims to highlight the practical decision-making value of untargeted metabolomics for the advancement of drug candidates in drug discovery/development including potentially identifying and validating novel therapeutic targets, creating alternative screening paradigms, facilitating the selection of specific and translational metabolite biomarkers, identifying metabolite signatures for the drug efficacy mechanism of action, and understanding potential drug-induced toxicity. The review provides an overview of the pharmaceutical process workflow to discover and develop new small molecule drugs followed by the metabolomics process workflow that is involved in conducting metabolomics studies. The pros and cons of the major components of the pharmaceutical and metabolomics workflows are reviewed and discussed. Finally, selected untargeted metabolomics literature examples, from primarily 2010 to 2016, are used to illustrate why, how, and where untargeted metabolomics can be integrated into the drug discovery/preclinical drug development process.
Drug Development
Metabolome
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Metabolomics is the term applied to the quantitative measurement of the metabolic response of living systems to patho-physiologic stimuli or genetic modification. As the scheme suggests, metabolomics studies rely on the analysis of the multitude of small molecules (metabolites) present in a biological system. Most commonly, metabolomics is heavily supported by mass spectrometry (MS) and nuclear magnetic resonance (NMR), as parallel technologies that provide an overview of the metabolome and high-power compound elucidation. By performing global metabolite profiling, also known as untargeted metabolomics, new discoveries linking cellular pathways to biological mechanism are being revealed and are shaping our understanding of cell biology, physiology and medicine. In this review, we discuss the advances in methodologies and applications of metabolomics. Ultimately, the number and chemical composition of metabolites to be studied are the defining attributes of any metabolomic experiment and the experiments will be designed with respect to sample preparation and choice of instrumentation.
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Metabolite profiling
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Importance of the field: Metabolomics is increasingly becoming an important field in the pharmaceutical industry to support the discovery and development of therapeutic agents. It allows the comprehensive and simultaneous profiling of hundreds of discrete biologically important molecules, including amino acids, sugars, lipids and exogenous substances from biological fluids and tissues. Metabolomics is the 'omics' field that most represents the interplay of internal biological regulation and external environmental influences on disease, thereby being of particular importance to disease mitigation and management.Areas covered in this review: Technological advances in the experimental work flow, analytical detection strategies and bioinformatics tools have enabled metabolomics studies to become increasingly comprehensive, robust and informative for the understanding of disease, drug action and the development of biomarkers. This review will focus on the practical aspects of metabolomics studies as they have been applied to the study of mammalian biological systems, specifically targeted to the steps of experimental design with regard to sample preparation, sample analysis and data analysis of both polar and non-polar metabolites.What the reader will gain: The reader will gain an overview of the field of metabolomics as it applies to drug development and the practical issues involved with experimental design. We will discuss the various methods of sample preparation and analysis as they apply to different classes of metabolites and highlight recent advances in the field that illustrate these methods.Take home message: The field of metabolomics is a rapidly expanding discipline that is being applied to various aspects of drug development. The large diversity of metabolites found in nature dictates that different methods be developed for the investigation of different classes of metabolites. As the field of metabolomics continues to mature, it is likely that it will play an increasingly important role in the characterization of disease and the future development of biomarkers to assess drug efficacy and safety.
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Metabolome
Biomarker Discovery
Identification
Relevance
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Metabolites are the end products of biological systems response to genetic control and/or environmental changes. Metabolomics,which study of total metabolites (metabolome),is an inevitable‘omics’following by genomics and proteomics. In this paper,metabolomics approaches including metabolites qualitative and quantitative determination,data acquisition and mining as well as their application in Botany such as target analysis,gene function determination,metabolite pathways and metabolic engineering,integrity Botany,signal transduction etc were reviewed.
Metabolome
Functional Genomics
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Metabolites are versatile bioactive molecules. They are not only the substrates and/or the products of enzymatic reactions but also act as the regulators in the systemic metabolism. Metabolomics is a high-throughput analytical strategy to qualify or quantify as many metabolites as possible in the metabolomes. It is an indispensable part of systems biology. The leading techniques in this field are mainly based on mass spectrometry and nuclear magnetic resonance spectroscopy. The metabolomic analysis has gained wide use in bioscience fields. In the tumor research arena, metabolomics can be employed to identify biomarkers for prediction, diagnosis, and prognosis. Chemotherapeutic effect evaluation and personalized medicine decision-making can also benefit from metabolomic analysis of patient biofluid or biopsy samples. Many cell-level studies can help in disease exploration. In this review, the basic features and principles of varied metabolomic analysis are introduced. The value of metabolomics in clinical and laboratory gastrointestinal cancer studies is discussed, especially for mass spectrometry applications. Besides, combined use of metabolomics and other tools to solve problems in cancer practice is briefly illustrated. In summary, metabolomics paves a new way to explore cancerous diseases in the light of small molecules.
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Expansive
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Abstract Mass spectrometry‐based metabolomics has become increasingly popular in molecular medicine. High‐definition mass spectrometry (MS), coupled with pattern recognition methods, have been carried out to obtain comprehensive metabolite profiling and metabolic pathway of large biological datasets. This sets the scene for a new and powerful diagnostic approach. Analysis of the key metabolites in body fluids has become an important part of improving disease diagnosis. With technological advances in analytical techniques, the ability to measure low‐molecular‐weight metabolites in bio‐samples provides a powerful platform for identifying metabolites that are uniquely correlated with a specific human disease. MS‐based metabolomics can lead to enhanced understanding of disease mechanisms and to new diagnostic markers and has a strong potential to contribute to improving early diagnosis of diseases. This review will highlight the importance and benefit with certain characteristic examples of MS‐metabolomics for identifying metabolic pathways and metabolites that accurately screen for potential diagnostic biomarkers of diseases. Copyright © 2015 John Wiley & Sons, Ltd.
Diagnostic biomarker
Biomarker Discovery
Metabolite profiling
Biological fluids
Profiling (computer programming)
Metabolome
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