The Consortium of Metabolomics Studies (COMETS): Metabolomics in 47 Prospective Cohort Studies

American Journal of Epidemiology, Journal Year: 2019, Volume and Issue: 188(6), P. 991 - 1012

Published: Jan. 30, 2019

The Consortium of Metabolomics Studies (COMETS) was established in 2014 to facilitate large-scale collaborative research on the human metabolome and its relationship with disease etiology, diagnosis, prognosis. COMETS comprises 47 cohorts from Asia, Europe, North America, South America that together include more than 136,000 participants blood metabolomics data samples collected 1985 2017. were provided by 17 different platforms, most frequently used labs being Metabolon, Inc. (14 cohorts), Broad Institute (15 Nightingale Health (11 cohorts). Participants have been followed for a median 23 years health outcomes including death, cancer, cardiovascular disease, diabetes, others; many studies are ongoing. Available exposure-related common clinical measurements behavioral factors, as well genome-wide genotype data. Two feasibility conducted evaluate comparability platforms cohorts. first study showed overlap between any 2 laboratories ranged 6 121 metabolites at 5 leading laboratories. second Spearman correlation comparing 111 overlapping captured Metabolon 0.79 (interquartile range, 0.56–0.89).

Language: Английский

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High-Speed Quantitative UPLC-MS Analysis of Multiple Amines in Human Plasma and Serum via Precolumn Derivatization with 6-Aminoquinolyl-N-hydroxysuccinimidyl Carbamate: Application to Acetaminophen-Induced Liver Failure

Analytical Chemistry, Journal Year: 2017, Volume and Issue: 89(4), P. 2478 - 2487

Published: Jan. 20, 2017

A targeted reversed-phase gradient UPLC-MS/MS assay has been developed for the quantification /monitoring of 66 amino acids and amino-containing compounds in human plasma serum using precolumn derivatization with 6-aminoquinolyl-N-hydroxysuccinimidyl carbamate (AccQTag Ultra). Derivatization target amines required minimal sample preparation resulted analytes excellent chromatographic mass spectrometric detection properties. The resulting method, which requires only 10 μL sample, provides reproducible robust separation 7.5 min, including baseline resolution isomers such as leucine isoleucine. validated 33 (predominantly acids) over a concentration range from 2 to 20 800 μM. Intra- interday accuracy between 0.05 15.6 0.78-13.7% precision 0.91 16.9% 2.12-15.9% were obtained. further biogenic can be monitored samples relative changes rather than quantification. Application derived healthy controls patients suffering acetaminophen (APAP, paracetamol)-induced acute liver failure (ALF) showed significant differences amounts aromatic branched chain groups well number other analytes, novel observation increased concentrations sarcosine ALF patients. properties assay, short analysis time, make it suitable high-throughput UPLC-ESI-MS/MS metabonomic clinical epidemiological environments.

Language: Английский

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New Potential Biomarkers for Chronic Kidney Disease Management—A Review of the Literature

International Journal of Molecular Sciences, Journal Year: 2020, Volume and Issue: 22(1), P. 43 - 43

Published: Dec. 22, 2020

The prevalence of chronic kidney disease (CKD) is increasing worldwide, and the mortality rate continues to be unacceptably high. biomarkers currently used in clinical practice are considered relevant when there already significant renal impairment compromising early use potentially successful therapeutic interventions. More sensitive specific detect CKD earlier on improve patients' prognoses an important unmet medical need. aim this review summarize recent literature new promising function, tubular lesions, endothelial dysfunction inflammation, auspicious findings from metabolomic studies field. Most studied require further validation large a broad range populations order implemented into routine management. A panel biomarkers, including damage, seems reasonable approach applied allow diagnosis better characterization based underlying etiologic process.

Language: Английский

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Metabolomics Approaches for the Diagnosis and Understanding of Kidney Diseases

Metabolites, Journal Year: 2019, Volume and Issue: 9(2), P. 34 - 34

Published: Feb. 14, 2019

Diseases of the kidney are difficult to diagnose and treat. This review summarises definition, cause, epidemiology treatment some these diseases including chronic disease, diabetic nephropathy, acute injury, cancer, transplantation polycystic diseases. Numerous studies have adopted a metabolomics approach uncover new small molecule biomarkers improve specificity sensitivity diagnosis biochemical mechanisms that may elucidate cause progression work includes description mass spectrometry-based approaches, currently available tools, emphasises findings from We included varied selection (disease, model, sample number, analytical platform) focused on metabolites which were commonly reported as discriminating features between disease control. These likely be robust indicators processes, therefore potential biomarkers, warranting further investigation.

Language: Английский

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A Prospective Analysis of Circulating Plasma Metabolites Associated with Ovarian Cancer Risk

Cancer Research, Journal Year: 2020, Volume and Issue: 80(6), P. 1357 - 1367

Published: Jan. 22, 2020

Ovarian cancer has few known risk factors, hampering identification of high-risk women. We assessed the association prediagnostic plasma metabolites (N = 420) with epithelial ovarian cancer, including both borderline and invasive tumors. A total 252 cases matched controls from Nurses' Health Studies were included. Multivariable logistic regression was used to estimate ORs 95% confidence intervals (CI), comparing 90th-10th percentile in metabolite levels, using permutation-based Westfall Young approach account for testing multiple correlated hypotheses. Weighted gene coexpression network analysis (WGCNA; n 10 modules) set enrichment (n 23 classes) also evaluated. An increase pseudouridine levels 10th 90th associated a 2.5-fold increased overall (OR 2.56; CI, 1.48-4.45; P 0.001/adjusted 0.15); similar observed serous/poorly differentiated tumors 176 cases; comparable OR 2.38; 1.33-4.32; 0.004/adjusted 0.55). For nonserous 34 cases), C36:2 phosphatidylcholine plasmalogen had strongest statistical associations 9.84; 2.89-37.82; < 0.07; 0.11; 0.03-0.35; 0.06, respectively). Five WGCNA modules 9 classes at FDR ≤ 0.20. Triacylglycerols (TAG) showed heterogeneity by tumor aggressiveness (case-only 0.0001). The TAG serous differed acyl carbon content saturation. In summary, this study suggests that may be novel factor TAGs important, particularly rapidly fatal tumors, differing structural features. SIGNIFICANCE: Pseudouridine represents potential triglycerides important

Language: Английский

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Harnessing Artificial Intelligence in Multimodal Omics Data Integration: Paving the Path for the Next Frontier in Precision Medicine

Annual Review of Biomedical Data Science, Journal Year: 2024, Volume and Issue: 7(1), P. 225 - 250

Published: May 20, 2024

The integration of multiomics data with detailed phenotypic insights from electronic health records marks a paradigm shift in biomedical research, offering unparalleled holistic views into and disease pathways. This review delineates the current landscape multimodal omics integration, emphasizing its transformative potential generating comprehensive understanding complex biological systems. We explore robust methodologies for ranging concatenation-based to transformation-based network-based strategies, designed harness intricate nuances diverse types. Our discussion extends incorporating large-scale population biobanks dissecting high-dimensional layers at single-cell level. underscores emerging role large language models artificial intelligence, anticipating their influence as near-future pivot approaches. Highlighting both achievements hurdles, we advocate concerted effort toward sophisticated models, fortifying foundation groundbreaking discoveries precision medicine.

Language: Английский

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Whole-exome sequencing identifies common and rare variant metabolic QTLs in a Middle Eastern population

Nature Communications, Journal Year: 2018, Volume and Issue: 9(1)

Published: Jan. 17, 2018

Metabolomics-genome-wide association studies (mGWAS) have uncovered many metabolic quantitative trait loci (mQTLs) influencing human individuality, though predominantly in European cohorts. By combining whole-exome sequencing with a high-resolution metabolomics profiling for highly consanguineous Middle Eastern population, we discover 21 common variant and 12 functional rare mQTLs, of which 45% are novel altogether. We fine-map 10 mQTLs to new metabolite ratio associations, 11 putative protein-altering variants. This is the first work report linked diseases and/or pharmacological targets Arab cohort, wide implications precision medicine East.

Language: Английский

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Branched-Chain Amino Acids as Critical Switches in Health and Disease

Hypertension, Journal Year: 2018, Volume and Issue: 72(5), P. 1012 - 1022

Published: Oct. 10, 2018

Language: Английский

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Metabolomics of Chronic Kidney Disease Progression: A Case-Control Analysis in the Chronic Renal Insufficiency Cohort Study

American Journal of Nephrology, Journal Year: 2016, Volume and Issue: 43(5), P. 366 - 374

Published: Jan. 1, 2016

<b><i>Background:</i></b> Whereas several longitudinal metabolomics studies have been conducted in individuals with normal estimated glomerular filtration rate (eGFR) at baseline, disease progression among established chronic kidney (CKD) has not rigorously examined. <b><i>Methods:</i></b> We performed a nested case-control study of rapid CKD the Chronic Renal Insufficiency Cohort Study, profiling baseline plasma from 200 each eGFR slope <-3 ml/min/1.73 m²/year (cases) or between -1 and +1 (controls), matched on proteinuria. To directly assess how modulates circulating metabolites, we profiled aorta renal vein 25 hospital-based individuals. <b><i>Results:</i></b> At cases controls had mean 41.7 ± 13.3 45.0 14.5 m², respectively. Ten metabolites were nominally associated logistic regression models adjusted for age, sex, race/ethnicity, hypertension, systolic diastolic blood pressure, diabetes, proteinuria; no metabolite achieved Bonferroni-adjusted significance threshold (p < 0.0003). In cross-sectional analysis, all 6 that higher than significantly baseline. By contrast, threonine, methionine arginine lower association eGFR. Furthermore, cohort underwent arteriovenous sampling, these 3 net released kidney. Combining into panel markers further strengthened their progression. <b><i>Conclusion:</i></b> Our results motivate interest arginine, threonine as potential indicators metabolic function prognosis.

Language: Английский

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Reliability of plasma polar metabolite concentrations in a large-scale cohort study using capillary electrophoresis-mass spectrometry

PLoS ONE, Journal Year: 2018, Volume and Issue: 13(1), P. e0191230 - e0191230

Published: Jan. 18, 2018

Background Cohort studies with metabolomics data are becoming more widespread, however, large-scale involving 10,000s of participants still limited, especially in Asian populations. Therefore, we started the Tsuruoka Metabolomics Study enrolling 11,002 community-dwelling adults Japan, and using capillary electrophoresis-mass spectrometry (CE-MS) liquid chromatography–mass spectrometry. The CE-MS method is highly amenable to absolute quantification polar metabolites, its reliability for measurement unclear. aim this study examine reproducibility validity measurements. In addition, presents concentrations metabolites human plasma, which can be used future as reference ranges a Japanese population. Methods Metabolomic profiling 8,413 fasting plasma samples were completed CE-MS, 94 structurally identified quantified. Quality control (QC) injected every ten assessed throughout analysis. Inter- intra-batch coefficients variation QC participant samples, technical intraclass correlation estimated. Passing-Bablok regression by on serum standard clinical chemistry assays was conducted creatinine uric acid. Results conclusions coefficient less than 20% 64 30% 80 out metabolites. Inter-batch 81 Estimated above 0.75 67 slope estimated 0.97 (95% confidence interval: 0.95, 0.98) 0.95 (0.92, 0.96) Compared published from other large cohort platforms, common platforms similar or better studies. These results show that our platform suitable conducting epidemiological

Language: Английский

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