Improved Accuracy and Reliability in Untargeted Analysis with LC-ESI-QTOF/MS1 by Ensemble Averaging DOI
Guillaume L. Erny,

Julia Nowak,

Michał Woźniakiewicz

et al.

Analytical Chemistry, Journal Year: 2025, Volume and Issue: unknown

Published: April 4, 2025

Untargeted liquid chromatography coupled with high-resolution mass spectrometry (LC-HRMS) is a powerful tool for comprehensive chemical analysis. Such techniques allow the detection and quantification of thousands compounds in sample. However, complexity variability data can introduce significant errors, impacting reliability results. This study investigates ensemble averaging to mitigate these errors improve signal-to-noise (S/N) ratios, feature detection, quality. In this work, 256 LC-qTOF/MS1 sets from analysis Morning Glory seeds were averaged generate merged sets. The numbers pooled files varied, number features, S/N ratio, accuracy precision accurate masses, relative intensities, migration time examined. It was proved that allows an increase up factor 10, standard deviation masses retention decreased by 10. Moreover, average features mined per set increased 1192 ± 129 original 4408 when all into one. Using known target compounds, benefits on quantitative investigated. measured theoretical intensities between [M+1]+H+, [M+2]+H+, [M+3]+H+ [M]+H+ isotopes alkaloids used. absolute error experimental below 3%, making isotopic pattern valid criterion confirming putative molecular formula. targeted approach recover information provides means. Peak lists fused obtain robust clustering recognizing (adducts, isotopes, fragments) generated common ionization chamber. Two hundred four clusters obtained, characterized two or more times differ less than 0.05 min similar response patterns.

Language: Английский

Mass spectrometry-based metabolomics in health and medical science: a systematic review DOI Creative Commons
Xiwu Zhang,

Qiu-Han Li,

Zuo-di Xu

et al.

RSC Advances, Journal Year: 2020, Volume and Issue: 10(6), P. 3092 - 3104

Published: Jan. 1, 2020

Metabolomics is the study of investigation small molecules derived from cellular and organism metabolism, which reflects outcomes complex network biochemical reactions in living systems.

Language: Английский

Citations

158
Precision of a Clinical Metabolomics Profiling Platform for Use in the Identification of Inborn Errors of Metabolism DOI Open Access

Lisa A. Ford,

Adam D. Kennedy,

Kelli D. Goodman

et al.

The Journal of Applied Laboratory Medicine, Journal Year: 2020, Volume and Issue: 5(2), P. 342 - 356

Published: Jan. 2, 2020

The application of whole-exome sequencing for the diagnosis genetic disease has paved way systems-based approaches in clinical laboratory. Here, we describe a metabolomics method screening metabolic diseases through analysis multi-pronged mass spectrometry platform. By simultaneously measuring hundreds metabolites single sample, offers comprehensive approach to identify perturbations across multiple biochemical pathways.We conducted single- and multi-day precision study on human plasma 4, multi-arm, high-throughput platforms.The average laboratory coefficient variation (CV) 4 platforms was between 9.3 11.5% (median, 6.5-8.4%), inter-assay CV ranged from 9.9 12.6% 7.0-8.3%) intra-assay 5.7 6.9% 3.5-4.4%). In relation patient sample testing, biomarkers associated with IEM disorders showed CVs that 0.2 11.0% analytical batches.This evaluation describes identical platforms, comprised each independent arms, reproducibility measurement key samples batches, providing evidence is robust reproducible patients inborn errors metabolism.

Language: Английский

Citations

133
Metabolomics for personalized medicine: the input of analytical chemistry from biomarker discovery to point-of-care tests DOI Creative Commons
Florence Castelli, Giulio Rosati, Christian Moguet

et al.

Analytical and Bioanalytical Chemistry, Journal Year: 2021, Volume and Issue: 414(2), P. 759 - 789

Published: Aug. 25, 2021

Abstract Metabolomics refers to the large-scale detection, quantification, and analysis of small molecules (metabolites) in biological media. Although metabolomics, alone or combined with other omics data, has already demonstrated its relevance for patient stratification frame research projects clinical studies, much remains be done move this approach practice. This is especially true perspective being applied personalized/precision medicine, which aims at stratifying patients according their risk developing diseases, tailoring medical treatments individual characteristics order improve efficacy limit toxicity. In review article, we discuss main challenges linked analytical chemistry that need addressed foster implementation metabolomics clinics use data produced by personalized medicine. First all, there are well-known issues related untargeted workflows levels production (lack standardization), metabolite identification (small proportion annotated features identified metabolites), processing (from automatic detection multi-omic integration) hamper inter-operability reusability data. Furthermore, outputs complex molecular signatures few tens metabolites, often abundance variations, obtained expensive laboratory equipment. It thus necessary simplify these so they can used field. last point, still poorly community, may crucial a near future increased availability societal demand participatory Graphical abstract

Language: Английский

Citations

79
Comparison of Untargeted Metabolomic Profiling vs Traditional Metabolic Screening to Identify Inborn Errors of Metabolism DOI Creative Commons
Ning Liu, Jing Xiao,

Charul Gijavanekar

et al.

JAMA Network Open, Journal Year: 2021, Volume and Issue: 4(7), P. e2114155 - e2114155

Published: July 12, 2021

Importance

Recent advances in newborn screening (NBS) have improved the diagnosis of inborn errors metabolism (IEMs); however, many potentially treatable IEMs are not included on NBS panels, nor they covered standard, first-line biochemical testing.

Objective

To examine utility untargeted metabolomics as a primary tool for by comparing diagnostic rate clinical with recommended traditional metabolic approach.

Design, Setting, and Participants

This cross-sectional study compares data from 4464 samples received 1483 unrelated families referred trio testing plasma amino acids, acylcarnitine profiling, urine organic acids (June 2014 to October 2018) 2000 consecutive 1807 (July February 2019) metabolomic at College American Pathologists Clinical Laboratory Improvement Amendments–certified genetics laboratory. Data analysis was performed September 2019 August 2020.

Exposures

Metabolic molecular tests genetic reference laboratory US available information each patient were assessed determine rate.

Main Outcomes Measures

The compared profiling context expanded NBS.

Results

Of cases screened approach, 912 patients (61.5%) male 1465 (98.8%) pediatric (mean [SD] age, 4.1 [6.0] years; range, 0-65 years). A total 19 identified IEMs, resulting 1.3% 14 detected, including 3 conditions Recommended Uniform Screening Panel undergoing 1059 (58.6%) male, 1665 (92.1%) 8.1 [10.4] 0-80 128 unique giving an overall 7.1%. In total, 70 different identified, 49 presently

Conclusions Relevance

These findings suggest that provided 6-fold higher yield conventional approach broader spectrum IEMs. Notably, expansion programs, approaches identify few disorders beyond those support capability should be considered initial evaluation disorders.

Language: Английский

Citations

59
Simultaneous Analysis of Organic Acids, Glycerol and Phenolic Acids in Wines Using Gas Chromatography-Mass Spectrometry DOI Creative Commons

Violeta García-Viñola,

Candela Ruiz-de-Villa, Jordi Gombau

et al.

Foods, Journal Year: 2024, Volume and Issue: 13(2), P. 186 - 186

Published: Jan. 5, 2024

Fermented beverages, particularly wines, exhibit variable concentrations of organic and phenolic acids, posing challenges in their accurate determination. Traditionally, enzymatic methods or chromatographic analyses, mainly high-performance liquid chromatography (HPLC), have been employed to quantify these compounds individually the grape must wine. However, analyses face limitations due high sugar content must. Meanwhile, found higher quantities red wines than white are typically analyzed using HPLC. This study presents a novel method for quantification acids (OAs), glycerol, musts wines. The approach involves liquid-liquid extraction with ethyl acetate, followed by sample derivatization analysis gas chromatography-mass spectrometry (GC-MS) selected ion monitoring (SIM) detection mode. results indicated successful all without need dilution. our showed that adding external standards was more suitable quantifying wine compounds, owing matrix effect. Furthermore, this is promising other metabolites present depending on extractability acetate. proposed (i) methoximation basic medium, (ii) acidification HCl, (iii) (iv) silyl analyze samples mode (SIM). In words, may be profiling (targeted) fingerprinting (untargeted) strategies classify according type winemaking process, grape, fermentation.

Language: Английский

Citations

11
Untargeted Metabolomics for Autism Spectrum Disorders: Current Status and Future Directions DOI Creative Commons
Kevin E. Glinton, Sarah H. Elsea

Frontiers in Psychiatry, Journal Year: 2019, Volume and Issue: 10

Published: Sept. 10, 2019

Autism spectrum disorders (ASDs) are a group of neurodevelopment characterized by childhood onset deficits in social communication and interaction. Although the exact etiology most cases ASDs is unknown, portion has been proposed to be associated with various metabolic abnormalities including mitochondrial dysfunction, cholesterol metabolism, folate abnormalities. Targeted biochemical testing like plasma amino acid acylcarnitine profiles have demonstrated limited utility helping diagnose manage such patients. Untargeted metabolomics emerged, however, as promising tool screening for underlying managing treatment means investigating possible novel biomarkers disorder. Here, we review principles methodology behind untargeted metabolomics, recent pilot studies utilizing this technology, areas which it may integrated into care children disorder future.

Language: Английский

Citations

63
Mass spectrometry based proteomics and metabolomics in personalized oncology DOI Creative Commons
Tomasz Kowalczyk, Michał Ciborowski, Joanna Kiśluk

et al.

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, Journal Year: 2020, Volume and Issue: 1866(5), P. 165690 - 165690

Published: Jan. 18, 2020

Language: Английский

Citations

59
Defining Blood Plasma and Serum Metabolome by GC-MS DOI Creative Commons
Olga I. Kiseleva, Ilya Y. Kurbatov, Ekaterina V. Ilgisonis

et al.

Metabolites, Journal Year: 2021, Volume and Issue: 12(1), P. 15 - 15

Published: Dec. 24, 2021

Metabolomics uses advanced analytical chemistry methods to analyze metabolites in biological samples. The most intensively studied samples are blood and its liquid components: plasma serum. Armed with equipment progressive software solutions, the scientific community has shown that small molecules’ roles living systems not limited traditional “building blocks” or “just fuel” for cellular energy. As a result, conclusions based on studying metabolome finding practical reflection molecular medicine better understanding of fundamental biochemical processes systems. This review is detailed protocol metabolomic analysis. However, it should support reader information about achievements whole process metabolic exploration human serum using mass spectrometry combined gas chromatography.

Language: Английский

Citations

46
The transition from genomics to phenomics in personalized population health DOI
James T. Yurkovich, Simon J. Evans, Noa Rappaport

et al.

Nature Reviews Genetics, Journal Year: 2023, Volume and Issue: 25(4), P. 286 - 302

Published: Dec. 13, 2023

Language: Английский

Citations

22
Current State and Future Perspectives on Personalized Metabolomics DOI Creative Commons
Oxana P. Trifonova, Dmitry L. Maslov, Elena E. Balashova

et al.

Metabolites, Journal Year: 2023, Volume and Issue: 13(1), P. 67 - 67

Published: Jan. 1, 2023

Metabolomics is one of the most promising ‘omics’ sciences for implementation in medicine by developing new diagnostic tests and optimizing drug therapy. Since metabolomics, end products biochemical processes an organism are studied, which under influence both genetic environmental factors, metabolomics analysis can detect any changes associated with lifestyle pathological processes. Almost every case-controlled study shows a high accuracy. Taking into account that already described nosologies, there prerequisites high-speed comprehensive metabolite will replace, near future, narrow range chemical analyses used today, medical community. However, despite perspectives personalized currently no FDA-approved tests. The well-known problem complexity data their interpretation end-users, addition to traditional need analytical methods address quality control, standardization, treatment reported review. Possible ways solve problems change situation introduction clinical practice, also discussed.

Language: Английский

Citations

20