MetaboAnalyst 5.0: narrowing the gap between raw spectra and functional insights

Nucleic Acids Research, Journal Year: 2021, Volume and Issue: 49(W1), P. W388 - W396

Published: April 28, 2021

Since its first release over a decade ago, the MetaboAnalyst web-based platform has become widely used for comprehensive metabolomics data analysis and interpretation. Here we introduce version 5.0, aiming to narrow gap from raw functional insights global based on high-resolution mass spectrometry (HRMS). Three modules have been developed help achieve this goal, including: (i) LC-MS Spectra Processing module which offers an easy-to-use pipeline that can perform automated parameter optimization resumable significantly lower barriers LC-MS1 spectra processing; (ii) Functional Analysis expands previous MS Peaks Pathways allow users intuitively select any peak groups of interest evaluate their enrichment potential functions as defined by metabolic pathways metabolite sets; (iii) Meta-Analysis combine multiple datasets obtained under complementary conditions or similar studies arrive at insights. There are many other new including weighted joint-pathway analysis, data-driven network batch effect correction, merging technical replicates, improved compound name matching, etc. The web interface, graphics underlying codebase also refactored improve performance user experience. At end session, now easily switch compatible more streamlined analysis. 5.0 is freely available https://www.metaboanalyst.ca.

Language: Английский

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Mass spectrometry-based metabolomics: a guide for annotation, quantification and best reporting practices

Nature Methods, Journal Year: 2021, Volume and Issue: 18(7), P. 747 - 756

Published: July 1, 2021

Language: Английский

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Metabolomics in cancer research and emerging applications in clinical oncology

CA A Cancer Journal for Clinicians, Journal Year: 2021, Volume and Issue: 71(4), P. 333 - 358

Published: May 13, 2021

Abstract Cancer has myriad effects on metabolism that include both rewiring of intracellular to enable cancer cells proliferate inappropriately and adapt the tumor microenvironment, changes in normal tissue metabolism. With recognition fluorodeoxyglucose‐positron emission tomography imaging is an important tool for management many cancers, other metabolites biological samples have been spotlight diagnosis, monitoring, therapy. Metabolomics global analysis small molecule like ‐omics technologies can provide critical information about state are otherwise not apparent. Here, authors review how therapies interact with at cellular systemic levels. An overview metabolomics provided a focus currently available they applied clinical translational research setting. The also discuss could be further leveraged future improve patients cancer.

Language: Английский

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Small molecule metabolites: discovery of biomarkers and therapeutic targets

Signal Transduction and Targeted Therapy, Journal Year: 2023, Volume and Issue: 8(1)

Published: March 20, 2023

Metabolic abnormalities lead to the dysfunction of metabolic pathways and metabolite accumulation or deficiency which is well-recognized hallmarks diseases. Metabolite signatures that have close proximity subject's phenotypic informative dimension, are useful for predicting diagnosis prognosis diseases as well monitoring treatments. The lack early biomarkers could poor serious outcomes. Therefore, noninvasive methods with high specificity selectivity desperately needed. Small molecule metabolites-based metabolomics has become a specialized tool biomarker pathway analysis, revealing possible mechanisms human various deciphering therapeutic potentials. It help identify functional related variation delineate biochemical changes indicators pathological damage prior disease development. Recently, scientists established large number profiles reveal underlying networks target exploration in biomedicine. This review summarized analysis on potential value small-molecule candidate metabolites clinical events, may better diagnosis, prognosis, drug screening treatment. We also discuss challenges need be addressed fuel next wave breakthroughs.

Language: Английский

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A metabolomics pipeline for the mechanistic interrogation of the gut microbiome

Nature, Journal Year: 2021, Volume and Issue: 595(7867), P. 415 - 420

Published: July 14, 2021

Language: Английский

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Ion mobility collision cross-section atlas for known and unknown metabolite annotation in untargeted metabolomics

Nature Communications, Journal Year: 2020, Volume and Issue: 11(1)

Published: Aug. 28, 2020

Abstract The metabolome includes not just known but also unknown metabolites; however, metabolite annotation remains the bottleneck in untargeted metabolomics. Ion mobility – mass spectrometry (IM-MS) has emerged as a promising technology by providing multi-dimensional characterizations of metabolites. Here, we curate an ion CCS atlas, namely AllCCS, and develop integrated strategy for using or chemical structures. AllCCS atlas covers vast structures with >5000 experimental records ~12 million calculated values >1.6 small molecules. We demonstrate high accuracy wide applicability medium relative errors 0.5–2% broad spectrum combined silico MS/MS spectra facilitates match substantially improves coverage both from biological samples. Together, is versatile resource that enables confident annotation, revealing comprehensive metabolic insights towards processes.

Language: Английский

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Comparison of Full-Scan, Data-Dependent, and Data-Independent Acquisition Modes in Liquid Chromatography–Mass Spectrometry Based Untargeted Metabolomics

Analytical Chemistry, Journal Year: 2020, Volume and Issue: 92(12), P. 8072 - 8080

Published: May 13, 2020

Full-scan, data-dependent acquisition (DDA), and data-independent (DIA) are the three common data modes in high resolution mass spectrometry-based untargeted metabolomics. It is an important yet underrated research topic on which mode more suitable for a given metabolomics application. In this work, we compared techniques using standard mixture of 134 endogenous metabolites human urine sample. Both hydrophilic interaction reversed-phase liquid chromatographic separation along with positive negative ionization were tested. sample generated consistent results. Full-scan able to capture largest number metabolic features, followed by DIA DDA (53.7% 64.8% respective features fewer average than full-scan). Comparing MS2 spectra DDA, quality higher dot product score 83.1% Urine(H), (spectra quantity) larger (on 97.8% urine). Moreover, comparison relative deviation distribution between shows consistency quantitative precision, exception showing minor disadvantage 19.8% 26.8% RSD < 5% full-scan DIA). terms preprocessing convenience, can be processed well-established software. contrast, several bioinformatic issues remain addressed processing development effective computational programs highly demanded.

Language: Английский

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Systemic and central nervous system metabolic alterations in Alzheimer’s disease

Alzheimer s Research & Therapy, Journal Year: 2019, Volume and Issue: 11(1)

Published: Nov. 28, 2019

Abstract Background Metabolic alterations, related to cerebral glucose metabolism, brain insulin resistance, and age-induced mitochondrial dysfunction, play an important role in Alzheimer’s disease (AD) on both the systemic central nervous system level. To study extent significance of these alterations AD, quantitative metabolomics was applied plasma cerebrospinal fluid (CSF) from clinically well-characterized AD patients cognitively healthy control subjects. The observed metabolic were associated with core pathological processes investigate their relation amyloid pathology tau-related neurodegeneration. Methods In a case-control clinical biomarker-confirmed ( n = 40) controls without 34) paired CSF samples, we performed profiling, i.e., untargeted targeted quantification. Targeted quantification focused identified deregulated pathways highlighted assay, i.e. TCA cycle, its anaplerotic pathways, as well neuroactive tryptophan kynurenine pathway. Results Concentrations several cycle beta-oxidation intermediates higher patients, whilst amino acid concentrations significantly lower. Similar energy metabolism CSF, together creatinine, which strongly correlated blood-brain barrier permeability. Alterations acids Amyloidβ1–42. catabolites, kynurenic quinolinic acid, showed which, other pathway intermediates, either Amyloidβ1–42, or tau phosphorylated Tau-181. Conclusions This revealed AD-associated dysregulation nutrient sensing oxidation CNS-specific (phospho)creatine degradation. specific association catabolites biomarkers suggests close relationship pathology. Our findings warrant validation independent, larger cohort studies further investigation factors such gender APOE genotype, groups, preclinical identify potential intervention targets.

Language: Английский

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Multi-omics integration in biomedical research – A metabolomics-centric review

Analytica Chimica Acta, Journal Year: 2020, Volume and Issue: 1141, P. 144 - 162

Published: Oct. 22, 2020

Language: Английский

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Metabolomics-centered mining of plant metabolic diversity and function: Past decade and future perspectives

Molecular Plant, Journal Year: 2022, Volume and Issue: 16(1), P. 43 - 63

Published: Sept. 16, 2022

Language: Английский

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