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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 -
Nature Reviews. Molecular Cell Biology Jul 2016Metabolomics, which is the profiling of metabolites in biofluids, cells and tissues, is routinely applied as a tool for biomarker discovery. Owing to innovative...
Metabolomics, which is the profiling of metabolites in biofluids, cells and tissues, is routinely applied as a tool for biomarker discovery. Owing to innovative developments in informatics and analytical technologies, and the integration of orthogonal biological approaches, it is now possible to expand metabolomic analyses to understand the systems-level effects of metabolites. Moreover, because of the inherent sensitivity of metabolomics, subtle alterations in biological pathways can be detected to provide insight into the mechanisms that underlie various physiological conditions and aberrant processes, including diseases.
Topics: Animals; Biomarkers; Humans; Metabolic Networks and Pathways; Metabolome; Metabolomics; Systems Biology
PubMed: 26979502
DOI: 10.1038/nrm.2016.25 -
Trends in Biotechnology Nov 2022Owing to recent advances in mass spectrometry (MS), tens to hundreds of proteins, lipids, and small molecules can be measured in single cells. The ability to... (Review)
Review
Owing to recent advances in mass spectrometry (MS), tens to hundreds of proteins, lipids, and small molecules can be measured in single cells. The ability to characterize the molecular heterogeneity of individual cells is necessary to define the full assortment of cell subtypes and identify their function. We review single-cell MS including high-throughput, targeted, mass cytometry-based approaches and antibody-free methods for broad profiling of the proteome and metabolome of single cells. The advantages and disadvantages of different methods are discussed, as well as the challenges and opportunities for further improvements in single-cell MS. These methods is being used in biomedicine in several applications including revealing tumor heterogeneity and high-content drug screening.
Topics: Lipids; Mass Spectrometry; Metabolome; Metabolomics; Proteome
PubMed: 35562238
DOI: 10.1016/j.tibtech.2022.04.004 -
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 -
Nucleic Acids Research Jan 2022The Human Metabolome Database or HMDB (https://hmdb.ca) has been providing comprehensive reference information about human metabolites and their associated biological,...
The Human Metabolome Database or HMDB (https://hmdb.ca) has been providing comprehensive reference information about human metabolites and their associated biological, physiological and chemical properties since 2007. Over the past 15 years, the HMDB has grown and evolved significantly to meet the needs of the metabolomics community and respond to continuing changes in internet and computing technology. This year's update, HMDB 5.0, brings a number of important improvements and upgrades to the database. These should make the HMDB more useful and more appealing to a larger cross-section of users. In particular, these improvements include: (i) a significant increase in the number of metabolite entries (from 114 100 to 217 920 compounds); (ii) enhancements to the quality and depth of metabolite descriptions; (iii) the addition of new structure, spectral and pathway visualization tools; (iv) the inclusion of many new and much more accurately predicted spectral data sets, including predicted NMR spectra, more accurately predicted MS spectra, predicted retention indices and predicted collision cross section data and (v) enhancements to the HMDB's search functions to facilitate better compound identification. Many other minor improvements and updates to the content, the interface, and general performance of the HMDB website have also been made. Overall, we believe these upgrades and updates should greatly enhance the HMDB's ease of use and its potential applications not only in human metabolomics but also in exposomics, lipidomics, nutritional science, biochemistry and clinical chemistry.
Topics: Databases, Genetic; Humans; Lipidomics; Mass Spectrometry; Metabolome; Metabolomics; User-Computer Interface
PubMed: 34986597
DOI: 10.1093/nar/gkab1062 -
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 -
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 -
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