Modern analytical techniques in metabolomics analysis

The Analyst, Journal Year: 2011, Volume and Issue: 137(2), P. 293 - 300

Published: Nov. 21, 2011

Metabolomics is the comprehensive assessment of endogenous metabolites and attempts to systematically identify quantify from a biological sample. Small-molecule have an important role in systems represent attractive candidates understand disease phenotypes. Metabolites diverse group low-molecular-weight structures including lipids, amino acids, peptides, nucleic organic vitamins, thiols carbohydrates, which makes global analysis difficult challenge. The recent rapid development range analytical platforms, GC, HPLC, UPLC, CE coupled MS NMR spectroscopy, could enable separation, detection, characterization quantification such related metabolic pathways. Owing complexity metabolome properties metabolites, no single platform can be applied detect all combined use modern instrumental approaches has unravelled ideal outcomes metabolomics, beneficial increase coverage detected that not achieved by single-analysis techniques. Integrated platforms been frequently used provide sensitive reliable detection thousands biofluid Continued these will accelerate widespread integration metabolomics into biology. Here, application each hyphenated technique discussed its strengths limitations are with selected illustrative examples; furthermore, this review comprehensively highlights integrated tools metabolomic research.

Language: Английский

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Quantitative Serum Nuclear Magnetic Resonance Metabolomics in Cardiovascular Epidemiology and Genetics

Circulation Cardiovascular Genetics, Journal Year: 2015, Volume and Issue: 8(1), P. 192 - 206

Published: Feb. 1, 2015

Metabolomics is becoming common in epidemiology due to recent developments quantitative profiling technologies and appealing results from their applications for understanding health disease. Our team has developed an automated high-throughput serum NMR metabolomics platform that provides molecular data on 14 lipoprotein subclasses, lipid concentrations composition, apolipoprotein A-I B, multiple cholesterol triglyceride measures, albumin, various fatty acids as well numerous low-molecular-weight metabolites, including amino acids, glycolysis related measures ketone bodies. The molar of these are obtained a single sample with costs comparable standard measurements. We have analyzed almost 250 000 samples around 100 epidemiological cohorts biobanks the new international set-up platforms will allow annual throughput more than samples. been used study type 1 2 diabetes etiology characterize reflections metabolic syndrome, long-term physical activity, diet metabolism. revealed biomarkers early atherosclerosis, diabetes, diabetic nephropathy, cardiovascular disease all-cause mortality. also combined genomics diverse studies. envision be incorporated routine large biobanks; this would make perfect sense both biological research cost point view – output over 200 vastly extend relevance collections many separate clinical chemistry assays redundant.

Language: Английский

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Genome-wide study for circulating metabolites identifies 62 loci and reveals novel systemic effects of LPA

Nature Communications, Journal Year: 2016, Volume and Issue: 7(1)

Published: March 23, 2016

Genome-wide association studies have identified numerous loci linked with complex diseases, for which the molecular mechanisms remain largely unclear. Comprehensive profiling of circulating metabolites captures highly heritable traits, can help to uncover metabolic pathophysiology underlying established disease variants. We conduct an extended genome-wide study genetic influences on 123 traits quantified by nuclear magnetic resonance metabolomics from up 24,925 individuals and identify eight novel amino acids, pyruvate fatty acids. The LPA locus link cardiovascular risk exemplifies how detailed may inform aetiology via extensive associations very-low-density lipoprotein triglyceride metabolism. Genetic fine mapping Mendelian randomization wide-spread causal effects lipoprotein(a) overall metabolism we assess potential pleiotropic consequences genetically elevated diverse morbidities electronic health-care records. Our findings strengthen argument safe LPA-targeted intervention reduce risk.

Language: Английский

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Metabolite Profiling and Cardiovascular Event Risk

Circulation, Journal Year: 2015, Volume and Issue: 131(9), P. 774 - 785

Published: Jan. 9, 2015

Background— High-throughput profiling of circulating metabolites may improve cardiovascular risk prediction over established factors. Methods and Results— We applied quantitative nuclear magnetic resonance metabolomics to identify the biomarkers for incident disease during long-term follow-up. Biomarker discovery was conducted in National Finnish FINRISK study (n=7256; 800 events). Replication incremental assessed Southall Brent Revisited (SABRE) (n=2622; 573 events) British Women’s Health Heart Study (n=3563; 368 In targeted analyses 68 lipids metabolites, 33 measures were associated with events at P <0.0007 after adjusting age, sex, blood pressure, smoking, diabetes mellitus, medication. When further routine lipids, 4 future meta-analyses: higher serum phenylalanine (hazard ratio per standard deviation, 1.18; 95% confidence interval, 1.12–1.24; =4×10 –10 ) monounsaturated fatty acid levels (1.17; 1.11–1.24; =1×10 –8 increased risk, while omega-6 acids (0.89; 0.84–0.94; =6×10 –5 docosahexaenoic (0.90; 0.86–0.95; =5×10 lower risk. A score incorporating these derived FINRISK. Risk estimates more accurate 2 validation cohorts (relative integrated discrimination improvement, 8.8% 4.3%), albeit not enhanced. classification particularly improved persons 5% 10% range (net reclassification, 27.1% 15.5%). associations corroborated mass spectrometry (n=671) Framingham Offspring (n=2289). Conclusions— Metabolite large prospective identified phenylalanine, acids, polyunsaturated as This substantiates value high-throughput biomarker assessment.

Language: Английский

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Genome-wide association study identifies multiple loci influencing human serum metabolite levels

Nature Genetics, Journal Year: 2012, Volume and Issue: 44(3), P. 269 - 276

Published: Jan. 29, 2012

Language: Английский

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Genome-wide association study identifies loci influencing concentrations of liver enzymes in plasma

Nature Genetics, Journal Year: 2011, Volume and Issue: 43(11), P. 1131 - 1138

Published: Oct. 16, 2011

Language: Английский

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Quantitative Serum Nuclear Magnetic Resonance Metabolomics in Large-Scale Epidemiology: A Primer on -Omic Technologies

American Journal of Epidemiology, Journal Year: 2017, Volume and Issue: 186(9), P. 1084 - 1096

Published: Jan. 30, 2017

Detailed metabolic profiling in large-scale epidemiologic studies has uncovered novel biomarkers for cardiometabolic diseases and clarified the molecular associations of established risk factors. A quantitative metabolomics platform based on nuclear magnetic resonance spectroscopy found widespread use, already over 400,000 blood samples. Over 200 measures are quantified per sample; addition to many routinely used epidemiology, method simultaneously provides fine-grained lipoprotein subclass quantification circulating fatty acids, amino gluconeogenesis-related metabolites, other molecules from multiple pathways. Here we focus applications quantifying epidemiology. We highlight characterization factors, use Mendelian randomization, key issues study design analyses also detail how integration data with genetics can enhance drug development. discuss why is becoming epidemiology biobanking. Although still novel, it seems likely that comprehensive biomarker will contribute etiologic understanding various abilities predict disease risks, potential translate into clinical settings.

Language: Английский

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Branched-Chain and Aromatic Amino Acids Are Predictors of Insulin Resistance in Young Adults

Diabetes Care, Journal Year: 2012, Volume and Issue: 36(3), P. 648 - 655

Published: Nov. 6, 2012

Branched-chain and aromatic amino acids are associated with the risk for future type 2 diabetes; however, underlying mechanisms remain elusive. We tested whether predict insulin resistance index in healthy young adults.Circulating isoleucine, leucine, valine, phenylalanine, tyrosine, six additional were quantified 1,680 individuals from population-based Cardiovascular Risk Young Finns Study (baseline age 32 ± 5 years; 54% women). Insulin was estimated by homeostasis model assessment (HOMA) at baseline 6-year follow-up. Amino acid associations HOMA of (HOMA-IR) glucose assessed using regression models adjusted established factors. further examined profiling could augment (defined as HOMA-IR >90th percentile) early adulthood.Isoleucine, tyrosine men follow-up, while women only phenylalanine predicted (P < 0.05). None other prospectively HOMA-IR. The sum branched-chain concentrations (odds ratio 2.09 [95% CI 1.38-3.17]; P = 0.0005); including score prediction did not improve discrimination.Branched-chain markers development young, normoglycemic adults, most pronounced men. These findings suggest that association diabetes is least partly mediated through resistance.

Language: Английский

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Lipids, Lipoproteins, and Metabolites and Risk of Myocardial Infarction and Stroke

Journal of the American College of Cardiology, Journal Year: 2018, Volume and Issue: 71(6), P. 620 - 632

Published: Feb. 1, 2018

Blood lipids are established risk factors for myocardial infarction (MI), but uncertainty persists about the relevance of lipids, lipoprotein particles, and circulating metabolites MI stroke subtypes. This study sought to investigate associations plasma metabolic markers with risks incident MI, ischemic (IS), intracerebral hemorrhage (ICH). In a nested case-control (912 1,146 IS, 1,138 ICH cases, 1,466 common control subjects) 30 79 years age in China Kadoorie Biobank, nuclear magnetic resonance spectroscopy measured 225 baseline samples. Logistic regression was used estimate adjusted odds ratios (ORs) 1-SD higher marker. Very low-, intermediate-, low-density particles were positively associated IS. High-density (HDL) inversely apart from small HDL. contrast, no ICH. Cholesterol large HDL IS (OR: 0.79 0.88, respectively), whereas cholesterol not 0.99 1.06, respectively). Triglycerides within all lipoproteins, including most similar pattern Glycoprotein acetyls, ketone bodies, glucose, docosahexaenoic acid 3 diseases. The showed concordant between Lipoproteins Within concentrations associated, triglyceride MI. acetyls several non–lipid-related

Language: Английский

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Biomarker Profiling by Nuclear Magnetic Resonance Spectroscopy for the Prediction of All-Cause Mortality: An Observational Study of 17,345 Persons

PLoS Medicine, Journal Year: 2014, Volume and Issue: 11(2), P. e1001606 - e1001606

Published: Feb. 25, 2014

In this study, Würtz and colleagues conducted high-throughput profiling of blood specimens in two large population-based cohorts order to identify biomarkers for all-cause mortality enhance risk prediction. The authors found that biomarker improved prediction the short-term death from all causes above established factors. However, further investigations are needed clarify biological mechanisms utility these guide screening prevention. Please see later article Editors' Summary

Language: Английский

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