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Journal of the American Society For... Dec 2016Metabolites are building blocks of cellular function. These species are involved in enzyme-catalyzed chemical reactions and are essential for cellular function. Upstream... (Review)
Review
Metabolites are building blocks of cellular function. These species are involved in enzyme-catalyzed chemical reactions and are essential for cellular function. Upstream biological disruptions result in a series of metabolomic changes and, as such, the metabolome holds a wealth of information that is thought to be most predictive of phenotype. Uncovering this knowledge is a work in progress. The field of metabolomics is still maturing; the community has leveraged proteomics experience when applicable and developed a range of sample preparation and instrument methodology along with myriad data processing and analysis approaches. Research focuses have now shifted toward a fundamental understanding of the biology responsible for metabolomic changes. There are several types of metabolomics experiments including both targeted and untargeted analyses. While untargeted, hypothesis generating workflows exhibit many valuable attributes, challenges inherent to the approach remain. This Critical Insight comments on these challenges, focusing on the identification process of LC-MS-based untargeted metabolomics studies-specifically in mammalian systems. Biological interpretation of metabolomics data hinges on the ability to accurately identify metabolites. The range of confidence associated with identifications that is often overlooked is reviewed, and opportunities for advancing the metabolomics field are described. Graphical Abstract ᅟ.
Topics: Animals; Chromatography, Liquid; Metabolome; Metabolomics; Tandem Mass Spectrometry
PubMed: 27624161
DOI: 10.1007/s13361-016-1469-y -
Nature Reviews. Microbiology Mar 2022Microbiotas are a malleable part of ecosystems, including the human ecosystem. Microorganisms affect not only the chemistry of their specific niche, such as the human... (Review)
Review
Microbiotas are a malleable part of ecosystems, including the human ecosystem. Microorganisms affect not only the chemistry of their specific niche, such as the human gut, but also the chemistry of distant environments, such as other parts of the body. Mass spectrometry-based metabolomics is one of the key technologies to detect and identify the small molecules produced by the human microbiota, and to understand the functional role of these microbial metabolites. This Review provides a foundational introduction to common forms of untargeted mass spectrometry and the types of data that can be obtained in the context of microbiome analysis. Data analysis remains an obstacle; therefore, the emphasis is placed on data analysis approaches and integrative analysis, including the integration of microbiome sequencing data.
Topics: Animals; Humans; Mass Spectrometry; Metabolome; Metabolomics; Microbiota
PubMed: 34552265
DOI: 10.1038/s41579-021-00621-9 -
Journal of Pharmaceutical and... Sep 2015Metabolomics is an emerging approach in a systems biology field. Due to continuous development in advanced analytical techniques and in bioinformatics, metabolomics has... (Review)
Review
Metabolomics is an emerging approach in a systems biology field. Due to continuous development in advanced analytical techniques and in bioinformatics, metabolomics has been extensively applied as a novel, holistic diagnostic tool in clinical and biomedical studies. Metabolome's measurement, as a chemical reflection of a current phenotype of a particular biological system, is nowadays frequently implemented to understand pathophysiological processes involved in disease progression as well as to search for new diagnostic or prognostic biomarkers of various organism's disorders. In this review, we discussed the research strategies and analytical platforms commonly applied in the metabolomics studies. The applications of the metabolomics in laboratory diagnostics in the last 5 years were also reviewed according to the type of biological sample used in the metabolome's analysis. We also discussed some limitations and further improvements which should be considered taking in mind potential applications of metabolomic research and practice.
Topics: Animals; Biomarkers; Clinical Laboratory Techniques; Computational Biology; Humans; Metabolome; Metabolomics
PubMed: 25577715
DOI: 10.1016/j.jpba.2014.12.017 -
Journal of Genetics and Genomics = Yi... Feb 2020Mass spectrometry (MS)-based omics technologies are now widely used to profile small molecules in multiple matrices to confer comprehensive snapshots of cellular... (Review)
Review
Mass spectrometry (MS)-based omics technologies are now widely used to profile small molecules in multiple matrices to confer comprehensive snapshots of cellular metabolic phenotypes. The metabolomes of cells, tissues, and organisms comprise a variety of molecules including lipids, amino acids, sugars, organic acids, and so on. Metabolomics mainly focus on the hydrophilic classes, while lipidomics has emerged as an independent omics owing to the complexities of the organismal lipidomes. The potential roles of lipids and small metabolites in disease pathogenesis have been widely investigated in various human diseases, but system-level understanding is largely lacking, which could be partly attributed to the insufficiency in terms of metabolite coverage and quantitation accuracy in current analytical technologies. While scientists are continuously striving to develop high-coverage omics approaches, integration of metabolomics and lipidomics is becoming an emerging approach to mechanistic investigation. Integration of metabolome and lipidome offers a complete atlas of the metabolic landscape, enabling comprehensive network analysis to identify critical metabolic drivers in disease pathology, facilitating the study of interconnection between lipids and other metabolites in disease progression. In this review, we summarize omics-based findings on the roles of lipids and metabolites in the pathogenesis of selected major diseases threatening public health. We also discuss the advantages of integrating lipidomics and metabolomics for in-depth understanding of molecular mechanism in disease pathogenesis.
Topics: Disease Progression; Humans; Lipid Metabolism; Lipidomics; Lipids; Mass Spectrometry; Metabolome; Metabolomics
PubMed: 32178981
DOI: 10.1016/j.jgg.2019.11.009 -
Mass Spectrometry Reviews Nov 2018In the past decade, advances in liquid chromatography-mass spectrometry (LC-MS) have revolutionized untargeted metabolomics analyses. By mining metabolomes more deeply,... (Review)
Review
In the past decade, advances in liquid chromatography-mass spectrometry (LC-MS) have revolutionized untargeted metabolomics analyses. By mining metabolomes more deeply, researchers are now primed to uncover key metabolites and their associations with diseases. The employment of untargeted metabolomics has led to new biomarker discoveries and a better mechanistic understanding of diseases with applications in precision medicine. However, many major pertinent challenges remain. First, compound identification has been poor, and left an overwhelming number of unidentified peaks. Second, partial, incomplete metabolomes persist due to factors such as limitations in mass spectrometry data acquisition speeds, wide-range of metabolites concentrations, and cellular/tissue/temporal-specific expression changes that confound our understanding of metabolite perturbations. Third, to contextualize metabolites in pathways and biology is difficult because many metabolites partake in multiple pathways, have yet to be described species specificity, or possess unannotated or more-complex functions that are not easily characterized through metabolomics analyses. From a translational perspective, information related to novel metabolite biomarkers, metabolic pathways, and drug targets might be sparser than they should be. Thankfully, significant progress has been made and novel solutions are emerging, achieved through sustained academic and industrial community efforts in terms of hardware, computational, and experimental approaches. Given the rapidly growing utility of metabolomics, this review will offer new perspectives, increase awareness of the major challenges in LC-MS metabolomics that will significantly benefit the metabolomics community and also the broader the biomedical community metabolomics aspire to serve.
Topics: Animals; Biomarkers; Chromatography, Liquid; Humans; Metabolic Networks and Pathways; Metabolome; Metabolomics; Tandem Mass Spectrometry
PubMed: 29486047
DOI: 10.1002/mas.21562 -
Metabolomics : Official Journal of the... Feb 2019Oral cancer is one of the most frequently occurring cancers. Metabolic reprogramming is an important hallmark of cancer. Metabolomics characterizes all the small... (Review)
Review
BACKGROUND
Oral cancer is one of the most frequently occurring cancers. Metabolic reprogramming is an important hallmark of cancer. Metabolomics characterizes all the small molecules in a biological sample, and a complete set of small molecules in such sample is referred as metabolome. Nuclear magnetic resonance spectroscopy and mass spectrometry are two widely used techniques in metabolomics studies. Increasing evidence demonstrates that metabolomics techniques can be used to explore the metabolic signatures in oral cancer. Elucidation of metabolic alterations in oral cancer is also important for the understanding of its pathological mechanisms.
AIM OF REVIEW
In this paper, we summarize the latest progress of metabolomics study in oral cancer and provide the suggestions for the future studies.
KEY SCIENTIFIC CONCEPTS OF REVIEW
The metabolomics studies in saliva, serum, and tumor tissues revealed the existence of metabolic signatures in bio-fluids and tissues of oral cancer, and several tumor-specific metabolites identified in individual study could discriminate oral cancer from healthy controls or precancerous lesions, which are potential biomarkers for the screening or early diagnosis of oral cancer. Metabolomics study of oral cancers in the future should aim to establish a routine procedure with high sensitivity, profile intracellular metabolites to find out the metabolic characteristics of tumor cells, and investigate the mechanism behind metabolomic alterations and the metabolic response of cancer cells to chemotherapy.
Topics: Biomarkers, Tumor; Humans; Magnetic Resonance Spectroscopy; Mass Spectrometry; Metabolome; Metabolomics; Mouth Neoplasms; Saliva; Serum
PubMed: 30830419
DOI: 10.1007/s11306-019-1483-8 -
Small Methods Jul 2022Mass spectrometry-based metabolomics has emerged as a powerful technique for biomedical research, although technical issues with its analytical precision and structural...
Mass spectrometry-based metabolomics has emerged as a powerful technique for biomedical research, although technical issues with its analytical precision and structural characterization remain. Herein, a robust non-targeted strategy for accurate quantitation and precise profiling of metabolomes is developed and applied to investigate plasma metabolic features associated with human aging. A comprehensive set of isotope-labeled standards (ISs) covering major metabolic pathways is incorporated to quantify polar metabolites. Matching rules to select ISs for calibration follow a primary criterion of minimal coefficients of variations (COVs). If minimal COVs between specific ISs for a particular metabolite fall within 5% window, a further selection of ISs is conducted based on structural similarities and proximity in retention time. The introduction and refined selection of appropriate ISs for quantitation reduces the COVs of 480 identified metabolites in quality control samples from 14.3% to 9.8% and facilitates identification of additional metabolite. Finally, the precise metabolomics approach reveals perturbations in a diverse array of metabolic pathways across aging that principally implicate steroid metabolism, amino acid metabolism, lipid metabolism, and purine metabolism, which allows the authors to draw correlates to the pathology of various age-related diseases. These findings provide clues for the prevention and treatment of these age-related diseases.
Topics: Aging; Humans; Mass Spectrometry; Metabolic Networks and Pathways; Metabolome; Metabolomics
PubMed: 35527334
DOI: 10.1002/smtd.202200130 -
Journal of Cachexia, Sarcopenia and... Feb 2018Cachexia is a multifactorial metabolic syndrome with high morbidity and mortality in patients with advanced cancer. The diagnosis of cancer cachexia depends on objective...
BACKGROUND
Cachexia is a multifactorial metabolic syndrome with high morbidity and mortality in patients with advanced cancer. The diagnosis of cancer cachexia depends on objective measures of clinical symptoms and a history of weight loss, which lag behind disease progression and have limited utility for the early diagnosis of cancer cachexia. In this study, we performed a nuclear magnetic resonance-based metabolomics analysis to reveal the metabolic profile of cancer cachexia and establish a diagnostic model.
METHODS
Eighty-four cancer cachexia patients, 33 pre-cachectic patients, 105 weight-stable cancer patients, and 74 healthy controls were included in the training and validation sets. Comparative analysis was used to elucidate the distinct metabolites of cancer cachexia, while metabolic pathway analysis was employed to elucidate reprogramming pathways. Random forest, logistic regression, and receiver operating characteristic analyses were used to select and validate the biomarker metabolites and establish a diagnostic model.
RESULTS
Forty-six cancer cachexia patients, 22 pre-cachectic patients, 68 weight-stable cancer patients, and 48 healthy controls were included in the training set, and 38 cancer cachexia patients, 11 pre-cachectic patients, 37 weight-stable cancer patients, and 26 healthy controls were included in the validation set. All four groups were age-matched and sex-matched in the training set. Metabolomics analysis showed a clear separation of the four groups. Overall, 45 metabolites and 18 metabolic pathways were associated with cancer cachexia. Using random forest analysis, 15 of these metabolites were identified as highly discriminating between disease states. Logistic regression and receiver operating characteristic analyses were used to create a distinct diagnostic model with an area under the curve of 0.991 based on three metabolites. The diagnostic equation was Logit(P) = -400.53 - 481.88 × log(Carnosine) -239.02 × log(Leucine) + 383.92 × log(Phenyl acetate), and the result showed 94.64% accuracy in the validation set.
CONCLUSIONS
This metabolomics study revealed a distinct metabolic profile of cancer cachexia and established and validated a diagnostic model. This research provided a feasible diagnostic tool for identifying at-risk populations through the detection of serum metabolites.
Topics: Aged; Cachexia; Female; Humans; Male; Metabolome; Metabolomics; Middle Aged; Neoplasms; Prognosis
PubMed: 29152916
DOI: 10.1002/jcsm.12246 -
Journal of Magnetic Resonance (San... Sep 2019NMR has been used to perform metabolic studies, metabolic profiling and metabolomics in biofluids and tissues for more than 40 years. This close connection between... (Review)
Review
NMR has been used to perform metabolic studies, metabolic profiling and metabolomics in biofluids and tissues for more than 40 years. This close connection between metabolic measurements and NMR has flourished because of NMR's many unique strengths for characterizing the chemical composition of complex mixtures. However, a number of other technologies, including mass spectrometry, have appeared in the past few years that are encroaching on NMR's dominance in metabolomics and metabolic studies. In this brief review, some of the current strengths and existing limitations of NMR-based metabolomics are highlighted. Additionally, a number of recent advances in NMR hardware, methodology and software are also described and these advancements are used to speculate about where NMR-based metabolomics is going, what needs to be done to make it more popular and how it will evolve in the next 5-10 years.
Topics: Animals; Humans; Metabolome; Metabolomics; Nuclear Magnetic Resonance, Biomolecular
PubMed: 31377153
DOI: 10.1016/j.jmr.2019.07.013 -
Current Molecular Medicine 2022Metabolomics is an omics approach of systems biology that involves the development and assessment of large-scale, comprehensive biochemical analysis tools for... (Review)
Review
Metabolomics is an omics approach of systems biology that involves the development and assessment of large-scale, comprehensive biochemical analysis tools for metabolites in biological systems. This review describes the metabolomics workflow and provides an overview of current analytic tools used for the quantification of metabolic profiles. We explain analytic tools such as mass spectrometry (MS), nuclear magnetic resonance (NMR) spectroscopy, ionization techniques, and approaches for data extraction and analysis.
Topics: Mass Spectrometry; Metabolome; Metabolomics; Systems Biology; Workflow
PubMed: 34923941
DOI: 10.2174/1566524022666211217102105