A Metabolite Array Technology for Precision Medicine

Xie, Guoxiang; Wang, Lu; Chen, Tianlu; Zhou, Kejun; Zhang, Zechuan; Li, Jiufeng; Sun, Beicheng; Guo, Yike; Wang, Xiaoning; Wang, Yixing; Zhang, Hua; Liu, Ping; Nicholson, Jeremy K.; Ge, Weihong; Wang, Jia

doi:10.1021/acs.analchem.0c04686

Cited by 128 publications

(98 citation statements)

References 27 publications

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“…The clinical diagnosis and enrolment criteria were detailed in our recently published report. 22 Test sets. A total of 48, 106, and 137 participants were enrolled independently from corresponding hospitals of the earlier studies (from January to September 2020).…”

Section: Discovery Setsmentioning

confidence: 99%

Altered bile acid glycine : taurine ratio in the progression of chronic liver disease

Chen

Zhou²,

Sun

et al. 2021

J of Gastro and Hepatol

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Background and Aim:The onset and progression of chronic liver disease (CLD) is a multistage process spanning years or several decades. Some bile acid (BA) features are identified as indicators for CLD progression. However, BAs are highly influenced by various factors and are stage and/or population specific. Emerging evidences demonstrated the association of structure of conjugated BAs and CLD progression. Here, we aimed to investigate the alteration of conjugated BAs and identify new features for CLD progression. Methods: Based on liquid chromatography-mass spectrometry platform, 15 BAs were quantified in 1883 participants including healthy controls and CLD patients (non-alcoholic fatty liver [NAFL], non-alcoholic steatohepatitis [NASH], fibrosis, cirrhosis, and three types of liver cancer). Logistic regression was used to construct diagnostic models. Model performances were evaluated in discovery and test sets by area under the receiver operating characteristic curve, sensitivity, specificity, accuracy, and kappa index. Results: Five BA glycine : taurine ratios were calculated, and glycocholic acid/taurocholic acid, glycodeoxycholic acid/taurodeoxycholic acid, and glycochenodeoxycholic acid/taurochenocholic acid were identified as candidates. Three diagnostic models were constructed for the differentiation of healthy control and early CLD (NAFL + NASH), early and advanced CLD (fibrosis + cirrhosis + liver cancer), and NAFL and NASH, respectively. The areas under the receiver operating characteristic curve of the models ranged from 0.91 to 0.97. The addition of age and gender improved model performances further. The alterations of the candidates and the performances of the diagnostic models were successfully validated by independent test sets (n = 291). Conclusions: Our findings revealed stage-specific BA perturbation patterns and provided new biomarkers and tools for the monitoring of liver disease progression.

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Section: Discovery Setsmentioning

confidence: 99%

Altered bile acid glycine : taurine ratio in the progression of chronic liver disease

Chen

Zhou²,

Sun

et al. 2021

J of Gastro and Hepatol

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“…An ultra-performance liquid chromatography coupled to tandem mass spectrometry (UPLC-MS/MS) system (ACQUITY UPLC-Xevo TQ-S, Waters Corp., Milford, MA, United States) was used to quantitatively determine 324 metabolites, including carbohydrates, amino acids, fatty acids, organic acids, and bile acids (Xie et al, 2021).…”

Section: Metabolomic Analysismentioning

confidence: 99%

Effects of Extreme Weight Loss on Cardiometabolic Health in Children With Metabolic Syndrome: A Metabolomic Study

et al. 2021

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Objectives: To evaluate the effect of extreme weight loss programs on circulating metabolites and their relationship with cardiometabolic health in children with metabolic syndrome.Methods: This study was a quasi-experimental design with a pretest and post-test. Thirty children with metabolic syndrome and aged 10–17years were recruited to an extreme weight loss program (i.e., exercise combined with diet control). The primary outcomes included plasma metabolites, body composition, and cardiometabolic risk factors. A total of 324 metabolites were quantitatively detected by an ultra-performance liquid chromatography coupled to tandem mass spectrometry system, and the variable importance in the projection (VIP) value of each metabolite was calculated by the orthogonal projection to latent structures discriminant analysis. The fold change (FC) and p value of each metabolite were used to screen differential metabolites with the following values: VIP>1, p value<0.05, and |log2FC|>0.25. Pathway enrichment and correlation analyses between metabolites and cardiometabolic risk factors were also performed.Result: A large effect size was observed, presenting a weight loss of −8.9kg (Cohen’s d=1.00, p<0.001), body mass index reduction of −3.3kg/m2 (Cohen’s d=1.47, p<0.001), and body fat percent reduction of −4.1 (%) (Cohen’s d=1.22, p<0.001) after the intervention. Similar improvements were found in total cholesterol (Cohen’s d=2.65, p<0.001), triglycerides (Cohen’s d=2.59, p<0.001), low-density lipoprotein cholesterol (Cohen’s d=2.81, p<0.001), glucose metabolism, and blood pressure. A total of 59 metabolites were changed after the intervention (e.g., aminoacyl-tRNA biosynthesis, glycine, serine, and threonine metabolism; nitrogen metabolism, tricarboxylic acid cycle, and phenylalanine, tyrosine, and tryptophan biosynthesis). The changes in metabolites (e.g., amino acids, fatty acids, organic acids, and carnitine) were related to lipid metabolism improvement (p<0.05). Organic acids and carnitines were associated with changes in the body composition (p<0.05).Conclusion: Exercise combined with dietary control improved the body composition and cardiometabolic health in children with metabolic syndrome, and these changes may be related to plasma metabolites.

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“…Metabolomics provides detailed information on molecular structure and can detect a wide range of metabolites simultaneously ( 27 ). The metabolomics kit used in this investigation was also used in our previous study ( 28 ), and provided quantitative data on 52 metabolites, which were mainly fatty acids and amino acids. An unsupervised dimensionality reduction method, namely principal component analysis, was used to investigate the internal characteristics of the dataset and eliminate singularities.…”

Section: Methodsmentioning

confidence: 99%

Metabolomics Analysis on Obesity-Related Obstructive Sleep Apnea After Weight Loss Management: A Preliminary Study

Huang

Zhong

et al. 2022

Front. Endocrinol.

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ObjectiveRoux-en-Y gastric bypass (RYGB) surgery is an effective type of weight loss management and may improve obesity-related obstructive sleep apnea (OSA). Obese subjects who meet the criteria for surgery with OSA were enrolled. We investigated the metabolomic effects of RYGB on OSA.MethodsClinical data, serum measurements including indices of glycolipid metabolism, and polysomnography (PSG) measurements were collected at baseline and 6 months after RYGB surgery. Metabolomic analysis was performed using ultra-performance liquid chromatography-mass spectrometry.ResultsA group of 37 patients with obesity, type 2 diabetes (T2DM) and suspected OSA were enrolled of which 27 were OSA subjects. After RYGB surgery, metabolic outcomes and sleep parameters were all significantly improved. The OSA remission group had lower valine, isoleucine, and C24:1(cis-15) levels, and higher trimethylamine N-oxide, hippurate, and indole-3-propionic acid levels after RYGB surgery. A combination of preoperative indices (age, apnea-hypopnea index (AHI), fasting C-peptide level, and hippurate level) predicted the RYGB effect size in obese patients with T2DM and OSA, with an area under receiver operating characteristic curve of 0.947, specificity of 82.4%, and sensitivity of 100%.ConclusionsRYGB surgery may significantly improve the metabolic status of patients with obesity, T2DM and OSA. A combination of preoperative indices (age, AHI, fasting C peptide level, and hippurate level) may be useful for predicting the effect size of RYGB in obese patients with T2DM and OSA. The mechanisms underlying OSA remission need to be explored.

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A Metabolite Array Technology for Precision Medicine

Cited by 128 publications

References 27 publications

Altered bile acid glycine : taurine ratio in the progression of chronic liver disease

Altered bile acid glycine : taurine ratio in the progression of chronic liver disease

Effects of Extreme Weight Loss on Cardiometabolic Health in Children With Metabolic Syndrome: A Metabolomic Study

Metabolomics Analysis on Obesity-Related Obstructive Sleep Apnea After Weight Loss Management: A Preliminary Study

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