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Cellular and Molecular Life Sciences :... Dec 2017Metabolomics is an analytical technique that investigates the small biochemical molecules present within a biological sample isolated from a plant, animal, or cultured... (Review)
Review
Metabolomics is an analytical technique that investigates the small biochemical molecules present within a biological sample isolated from a plant, animal, or cultured cells. It can be an extremely powerful tool in elucidating the specific metabolic changes within a biological system in response to an environmental challenge such as disease, infection, drugs, or toxins. A historically difficult step in the metabolomics pipeline is in data interpretation to a meaningful biological context, for such high-variability biological samples and in untargeted metabolomics studies that are hypothesis-generating by design. One way to achieve stronger biological context of metabolomic data is via the use of cultured cell models, particularly for mammalian biological systems. The benefits of in vitro metabolomics include a much greater control of external variables and no ethical concerns. The current concerns are with inconsistencies in experimental procedures and level of reporting standards between different studies. This review discusses some of these discrepancies between recent studies, such as metabolite extraction and data normalisation. The aim of this review is to highlight the importance of a standardised experimental approach to any cultured cell metabolomics study and suggests an example procedure fully inclusive of information that should be disclosed in regard to the cell type/s used and their culture conditions. Metabolomics of cultured cells has the potential to uncover previously unknown information about cell biology, functions and response mechanisms, and so the accurate biological interpretation of the data produced and its ability to be compared to other studies should be considered vitally important.
Topics: Animals; Cell Line; Humans; Mammals; Metabolome; Metabolomics; Research Design
PubMed: 28669031
DOI: 10.1007/s00018-017-2582-1 -
Methods in Molecular Biology (Clifton,... 2019Drug discovery is an extremely difficult and challenging endeavor with a very high failure rate. The task of identifying a drug that is safe, selective, and effective is...
Drug discovery is an extremely difficult and challenging endeavor with a very high failure rate. The task of identifying a drug that is safe, selective, and effective is a daunting proposition because disease biology is complex and highly variable across patients. Metabolomics enables the discovery of disease biomarkers, which provides insights into the molecular and metabolic basis of disease and may be used to assess treatment prognosis and outcome. In this regard, metabolomics has evolved to become an important component of the drug discovery process to resolve efficacy and toxicity issues and as a tool for precision medicine. A detailed description of an experimental protocol is presented that outlines the application of NMR metabolomics to the drug discovery pipeline. This includes (1) target identification by understanding the metabolic dysregulation in diseases, (2) predicting the mechanism of action of newly discovered or existing drug therapies, (3) and using metabolomics to screen a chemical lead to assess biological activity. Unlike other OMICS approaches, the metabolome is "fragile" and may be negatively impacted by improper sample collection, storage, and extraction procedures. Similarly, biologically irrelevant conclusions may result from incorrect data collection, preprocessing or processing procedures, or the erroneous use of univariate and multivariate statistical methods. These critical concerns are also addressed in the protocol.
Topics: Animals; Bacteria; Biomarkers; Drug Discovery; Drug Evaluation, Preclinical; Humans; Magnetic Resonance Spectroscopy; Metabolome; Metabolomics; Mice; Models, Biological; Pharmaceutical Preparations
PubMed: 31463851
DOI: 10.1007/978-1-4939-9690-2_16 -
BMC Bioinformatics Jun 2023Metabolomics is a dynamic tool for elucidating biochemical changes in human health and disease. Metabolic profiles provide a close insight into physiological states and... (Review)
Review
Metabolomics is a dynamic tool for elucidating biochemical changes in human health and disease. Metabolic profiles provide a close insight into physiological states and are highly volatile to genetic and environmental perturbations. Variation in metabolic profiles can inform mechanisms of pathology, providing potential biomarkers for diagnosis and assessment of the risk of contracting a disease. With the advancement of high-throughput technologies, large-scale metabolomics data sources have become abundant. As such, careful statistical analysis of intricate metabolomics data is essential for deriving relevant and robust results that can be deployed in real-life clinical settings. Multiple tools have been developed for both data analysis and interpretations. In this review, we survey statistical approaches and corresponding statistical tools that are available for discovery of biomarkers using metabolomics.
Topics: Humans; Metabolomics; Metabolome; Biomarkers; Biomedical Research; Data Analysis
PubMed: 37322419
DOI: 10.1186/s12859-023-05383-0 -
Circulation Research Feb 2022Despite the well-known sex dimorphism in cardiovascular disease traits, the exact genetic, molecular, and cellular underpinnings of these differences are not well... (Review)
Review
Despite the well-known sex dimorphism in cardiovascular disease traits, the exact genetic, molecular, and cellular underpinnings of these differences are not well understood. A growing body of evidence currently points at the links between cardiovascular disease traits and the genome, epigenome, transcriptome, and metabolome. However, the sex-specific differences in these links remain largely unstudied due to challenges in bioinformatic methods, inadequate statistical power, analytic costs, and paucity of valid experimental models. This review article provides an overview of the literature on sex differences in genetic architecture, heritability, epigenetic changes, transcriptomic signatures, and metabolomic profiles in relation to cardiovascular disease traits. We also review the literature on the associations between sex hormones and cardiovascular disease traits and discuss the potential mechanisms underlying these associations, focusing on human studies.
Topics: Cardiovascular Diseases; Epigenesis, Genetic; Epigenome; Female; Humans; Male; Metabolome; Metabolomics; Sex Characteristics
PubMed: 35175841
DOI: 10.1161/CIRCRESAHA.121.319891 -
Pharmacogenomics Dec 2018
Review
Topics: Genome, Human; Genomics; Humans; Metabolome; Metabolomics; Pharmacogenetics
PubMed: 30398072
DOI: 10.2217/pgs-2018-0155 -
Analytical and Bioanalytical Chemistry Nov 2023Single-cell (SC) analysis offers new insights into the study of fundamental biological phenomena and cellular heterogeneity. The superior sensitivity, high throughput,... (Review)
Review
Single-cell (SC) analysis offers new insights into the study of fundamental biological phenomena and cellular heterogeneity. The superior sensitivity, high throughput, and rich chemical information provided by mass spectrometry (MS) allow MS to emerge as a leading technology for molecular profiling of SC omics, including the SC metabolome, lipidome, and proteome. However, issues such as ionization suppression, low concentration, and huge span of dynamic concentrations of SC components lead to poor MS response for certain types of molecules. It is noted that chemical tagging/derivatization has been adopted in SCMS analysis, and this strategy has been proven an effective solution to circumvent these issues in SCMS analysis. Herein, we review the basic principle and general strategies of chemical tagging/derivatization in SCMS analysis, along with recent applications of chemical derivatization to single-cell metabolomics and multiplexed proteomics, as well as SCMS imaging. Furthermore, the challenges and opportunities for the improvement of chemical derivatization strategies in SCMS analysis are discussed.
Topics: Mass Spectrometry; Metabolomics; Metabolome; Proteomics; Lipidomics
PubMed: 37466681
DOI: 10.1007/s00216-023-04850-0 -
Methods in Molecular Biology (Clifton,... 2022Cancer cells possess an elevated demand for nutrients and metabolites due to their uncontrolled proliferation and need to survive in unfavorable conditions. Autophagy is...
Cancer cells possess an elevated demand for nutrients and metabolites due to their uncontrolled proliferation and need to survive in unfavorable conditions. Autophagy is a conservative degradation pathway that counters lack of nutrients and provides organelle and protein quality control, beyond maintenance of cellular metabolism.Mass spectrometry-based metabolomics is a powerful tool to study the metabolome of a cell. Such analysis requires proper sample preparation including the extraction of metabolites. Here, we provide a protocol for the extraction of metabolites from adherent cancer cells suitable for global metabolome profiling by mass spectrometry.
Topics: Mass Spectrometry; Metabolome; Metabolomics; Neoplasms
PubMed: 34973001
DOI: 10.1007/978-1-0716-2071-7_20 -
Mass Spectrometry Reviews 2014The metabolome is the set of small molecular mass compounds found in biological media, and metabolomics, which refers to as the analysis of metabolome in a given... (Review)
Review
The metabolome is the set of small molecular mass compounds found in biological media, and metabolomics, which refers to as the analysis of metabolome in a given biological condition, deals with the large scale detection and quantification of metabolites in biological media. It is a data driven and multidisciplinary approach combining analytical chemistry for data acquisition, and biostatistics, informatics and biochemistry for mining and interpretation of these data. Since the middle of the 2000s, high resolution mass spectrometry is widely used in metabolomics, mainly because the detection and identification of metabolites are improved compared to low resolution instruments. As the field of HRMS is quickly and permanently evolving, the aim of this work is to review its use in different aspects of metabolomics, including data acquisition, metabolite annotation, identification and quantification. At last, we would like to show that, thanks to their versatility, HRMS instruments are the most appropriate to achieve optimal metabolome coverage, at the border of other omics fields such as lipidomics and glycomics.
Topics: Animals; Gene Expression Profiling; Humans; Mass Spectrometry; Metabolic Networks and Pathways; Metabolome; Metabolomics; Microchemistry; Proteome
PubMed: 24288070
DOI: 10.1002/mas.21401 -
Advances in Experimental Medicine and... 2021Most microbe-associated infectious diseases severely affect human health. However, clinical diagnosis of pathogenic diseases remains challenging due to the lack of...
Most microbe-associated infectious diseases severely affect human health. However, clinical diagnosis of pathogenic diseases remains challenging due to the lack of specific and highly reliable methods. To better understand the diagnosis, pathogenesis, and treatment of these diseases, systems biology-driven metabolomics goes beyond the annotated phenotype and better targets the functions than conventional approaches. As a novel strategy for analysis of metabolomes in microbes, microbial metabolomics has been recently used to study many diseases, such as obesity, urinary tract infection (UTI), and hepatitis C. In this chapter, we attempt to introduce various microbial metabolomics methods to better interpret the microbial metabolism underlying a diversity of infectious diseases and inspire scientists to pay more attention to microbial metabolomics, enabling broadly and efficiently its translational applications to infectious diseases, from molecular diagnosis to therapeutic discovery.
Topics: Humans; Metabolome; Metabolomics; Systems Biology; Urinary Tract Infections
PubMed: 33791977
DOI: 10.1007/978-3-030-51652-9_7 -
Journal of Pharmaceutical and... Oct 2023Cerebrovascular stenosis (CVS) is the main cause of ischemic stroke, which greatly threatens human life. Hence, it's important to perform early screenings for CVS....
Cerebrovascular stenosis (CVS) is the main cause of ischemic stroke, which greatly threatens human life. Hence, it's important to perform early screenings for CVS. Metabolomics is an emerging omics approach that has great advantages in disease screening and diagnosis. Therefore, we aim to elucidate the correlation between CVS and metabolomics, which can aid in conducting CVS screening at an early stage. Patients with CVS in Beijing Hospital were included in the study. A total of 36 participants, including 18 patients diagnosed with CVS and 18 healthy individuals, were recruited at Beijing Hospital between May 2022 and October 2021. The serum samples were analyzed for liquid chromatography-tandem mass spectrometry (LC-MS/MS). Then, multivariate statistical methods, including principal component analysis (PCA), partial least squares-discriminant analysis (PLS-DA) and orthogonal partial least squares-discriminant analysis (OPLS-DA) were performed. Differential metabolites were obtained and demonstrated by volcano plot and heatmap. The study recruited 36 participants, including 18 patients with CVS and 18 healthy participants. A total of 150 metabolites were identified. Multivariate statistical analysis revealed significant differences between patients and healthy participants. Furthermore, 30 serum metabolites levels differed significantly between two groups. Differential metabolites were enriched in phenylalanine, tyrosine, and tryptophan biosynthesis; primary bile acid biosynthesis, and other pathways. This study identified differential metabolites in patients with CVS and elucidated the relevant metabolic pathways. Thus, these findings aid in the study of the pathogenesis of CVS and its early diagnosis. DATA AVAILABILITY STATEMENT: The datasets generated for this study are available on request to the corresponding author.
Topics: Humans; Chromatography, Liquid; Tandem Mass Spectrometry; Constriction, Pathologic; Metabolomics; Metabolome; Biomarkers
PubMed: 37527609
DOI: 10.1016/j.jpba.2023.115608