986 results found
Hedjazi L, Gauguier D, Zalloua PA, et al., 2015, MQTL.NMR: An integrated suite for genetic mapping of quantitative variations of <sup>1</sup>H NMR-based metabolic profiles, Analytical Chemistry, Vol: 87, Pages: 4377-4384, ISSN: 0003-2700
High-throughput <sup>1</sup>H nuclear magnetic resonance (NMR) is an increasingly popular robust approach for qualitative and quantitative metabolic profiling, which can be used in conjunction with genomic techniques to discover novel genetic associations through metabotype quantitative trait locus (mQTL) mapping. There is therefore a crucial necessity to develop specialized tools for an accurate detection and unbiased interpretability of the genetically determined metabolic signals. Here we introduce and implement a combined chemoinformatic approach for objective and systematic analysis of untargeted <sup>1</sup>H NMR-based metabolic profiles in quantitative genetic contexts. The R/Bioconductor mQTL.NMR package was designed to (i) perform a series of preprocessing steps restoring spectral dependency in collinear NMR data sets to reduce the multiple testing burden, (ii) carry out robust and accurate mQTL mapping in human cohorts as well as in rodent models, (iii) statistically enhance structural assignment of genetically determined metabolites, and (iv) illustrate results with a series of visualization tools. Built-in flexibility and implementation in the powerful R/Bioconductor framework allow key preprocessing steps such as peak alignment, normalization, or dimensionality reduction to be tailored to specific problems. The mQTL.NMR package is freely available with its source code through the Comprehensive R/Bioconductor repository and its own website (http://www.ican-institute.org/tools/). It represents a significant advance to facilitate untargeted metabolomic data processing and quantitative analysis and their genetic mapping.
Wu Q, Li JV, Seyfried F, et al., 2015, Metabolic phenotype-microRNA data fusion analysis of the systemic consequences of Roux-en-Y gastric bypass surgery., International Journal of Obesity, Vol: 2015, Pages: 1126-1134, ISSN: 1476-5497
Background/Objectives: Bariatric surgery offers sustained dramatic weight loss and often remission of type 2 diabetes, yet the mechanisms of establishment of these health benefits are not clear.Subjects/MethodsWe mapped the co-ordinated systemic responses of gut hormones, the circulating miRNAome and the metabolome in a rat model of Roux-en-Y gastric bypass (RYGB) surgery. Results: The response of circulating miRNAs to RYGB was striking and selective. Analysis of 14 significantly altered circulating miRNAs within a pathway context was suggestive of modulation of signalling pathways including G protein signalling, neurodegeneration, inflammation, and growth and apoptosis responses. Concomitant alterations in the metabolome indicated increased glucose transport, accelerated glycolysis and inhibited gluconeogenesis in the liver. Of particular significance, we show significantly decreased circulating miRNA-122 levels and a more modest decline in hepatic levels, following surgery. In mechanistic studies, manipulation of miRNA-122 levels in a cell model induced changes in the activity of key enzymes involved in hepatic energy metabolism, glucose transport, glycolysis, TCA cycle, pentose phosphate shunt, fatty acid oxidation and gluconeogenesis, consistent with the findings of the in vivo surgery-mediated responses, indicating the powerful homeostatic activity of the miRNAs. Conclusions: The close association between energy metabolism, neuronal signalling and gut microbial metabolites derived from the circulating miRNA, plasma, urine and liver metabolite and gut hormone correlations further supports an enhanced gut-brain signaling, which we suggest is hormonally mediated by both traditional gut hormones and miRNAs. This transomic approach to map the crosstalk between the circulating miRNAome and metabolome offers opportunities to understand complex systems biology within a disease and interventional treatment setting.International Journal of Obesity accepted article previe
MacIntyre DA, Chandiramani M, Lee YS, et al., 2015, The vaginal microbiome during pregnancy and the postpartum period in a European population, Scientific Reports, Vol: 5, ISSN: 2045-2322
The composition and structure of the pregnancy vaginal microbiome may influence susceptibility to adverse pregnancy outcomes. Studies on the pregnant vaginal microbiome have largely been limited to Northern American populations. Using MiSeq sequencing of 16S rRNA gene amplicons, we characterised the vaginal microbiota of a mixed British cohort of women (n = 42) who experienced uncomplicated term delivery and who were sampled longitudinally throughout pregnancy (8–12, 20–22, 28–30 and 34–36 weeks gestation) and 6 weeks postpartum. We show that vaginal microbiome composition dramatically changes postpartum to become less Lactobacillus spp. dominant with increased alpha-diversity irrespective of the community structure during pregnancy and independent of ethnicity. While the pregnancy vaginal microbiome was characteristically dominated by Lactobacillus spp. and low alpha-diversity, unlike Northern American populations, a significant number of pregnant women this British population had a L. jensenii-dominated microbiome characterised by low alpha-diversity. L. jensenii was predominantly observed in women of Asian and Caucasian ethnicity whereas L. gasseri was absent in samples from Black women. This study reveals new insights into biogeographical and ethnic effects upon the pregnancy and postpartum vaginal microbiome and has important implications for future studies exploring relationships between the vaginal microbiome, host health and pregnancy outcomes.
Vorkas PA, Shalhoub J, Isaac G, et al., 2015, Metabolic Phenotyping of Atherosclerotic Plaques Reveals Latent Associations between Free Cholesterol and Ceramide Metabolism in Atherogenesis., Journal of Proteome Research, Vol: 14, Pages: 1389-1399, ISSN: 1535-3907
Current optimum medical treatments have had limited success in the primary prevention of cardiovascular events, underscoring the need for new pharmaceutical targets and enhanced understanding of mechanistic metabolic dysregulation. Here, we use a combination of novel metabolic profiling methodologies, based on ultra-performance liquid chromatography coupled to mass spectrometry (UPLC-MS) followed by chemometric modeling, data integration, and pathway mapping, to create a systems-level metabolic atlas of atherogenesis. We apply this workflow to compare arterial tissue incorporating plaque lesions to intimal thickening tissue (immediate preplaque stage). We find changes in several metabolite species consistent with well-established pathways in atherosclerosis, such as the cholesterol, purine, pyrimidine, and ceramide pathways. We then illustrate differential levels of previously unassociated lipids to atherogenesis, namely, phosphatidylethanolamine-ceramides (t-test p-values: 3.8 × 10(-6) to 9.8 × 10(-12)). Most importantly, these molecules appear to be interfacing two pathways recognized for their involvement in atherosclerosis: ceramide and cholesterol. Furthermore, we show that β-oxidation intermediates (i.e., acylcarnitines) manifest a pattern indicating truncation of the process and overall dysregulation of fatty acid metabolism and mitochondrial dysfunction. We develop a metabolic framework that offers the ability to map significant statistical associations between detected biomarkers. These dysregulated molecules and consequent pathway modulations may provide novel targets for pharmacotherapeutic intervention.
Vorkas PA, Isaac G, Anwar MA, et al., 2015, Untargeted UPLC-MS Profiling Pipeline to Expand Tissue Metabolome Coverage: Application to Cardiovascular Disease., Analytical Chemistry, Vol: 87, Pages: 4184-4193, ISSN: 1086-4377
Metabolic profiling studies aim to achieve broad metabolome coverage in specific biological samples. However, wide metabolome coverage has proven difficult to achieve, mostly because of the diverse physicochemical properties of small molecules, obligating analysts to seek multiplatform and multimethod approaches. Challenges are even greater when it comes to applications to tissue samples, where tissue lysis and metabolite extraction can induce significant systematic variation in composition. We have developed a pipeline for obtaining the aqueous and organic compounds from diseased arterial tissue using two consecutive extractions, followed by a different untargeted UPLC-MS analysis method for each extract. Methods were rationally chosen and optimized to address the different physicochemical properties of each extract: hydrophilic interaction liquid chromatography (HILIC) for the aqueous extract and reversed-phase chromatography for the organic. This pipeline can be generic for tissue analysis as demonstrated by applications to different tissue types. The experimental setup and fast turnaround time of the two methods contributed toward obtaining highly reproducible features with exceptional chromatographic performance (CV % < 0.5%), making this pipeline suitable for metabolic profiling applications. We structurally assigned 226 metabolites from a range of chemical classes (e.g., carnitines, α-amino acids, purines, pyrimidines, phospholipids, sphingolipids, free fatty acids, and glycerolipids) which were mapped to their corresponding pathways, biological functions and known disease mechanisms. The combination of the two untargeted UPLC-MS methods showed high metabolite complementarity. We demonstrate the application of this pipeline to cardiovascular disease, where we show that the analyzed diseased groups (n = 120) of arterial tissue could be distinguished based on their metabolic profiles.
Cogswell ME, Maalouf J, Elliott P, et al., 2015, Use of Urine Biomarkers to Assess Sodium Intake: Challenges and Opportunities, ANNUAL REVIEW OF NUTRITION, VOL 35, Editors: Bowman, Stover, Publisher: ANNUAL REVIEWS, Pages: 349-+
Chang KL, Pee HN, Tan WP, et al., 2015, Metabolic Profiling of CHO-A beta PP695 Cells Revealed Mitochondrial Dysfunction Prior to Amyloid-beta Pathology and Potential Therapeutic Effects of Both PPAR gamma and PPAR alpha Agonisms for Alzheimer's Disease, JOURNAL OF ALZHEIMERS DISEASE, Vol: 44, Pages: 215-231, ISSN: 1387-2877
Rainville PD, Murphy JP, Tomany M, et al., 2015, An integrated ceramic, micro-fluidic device for the LC/MS/MS analysis of pharmaceuticals in plasma, ANALYST, Vol: 140, Pages: 5546-5556, ISSN: 0003-2654
Villasenor A, Kinross JM, Li JV, et al., 2014, H-1 NMR Global Metabolic Phenotyping of Acute Pancreatitis in the Emergency Unit, JOURNAL OF PROTEOME RESEARCH, Vol: 13, Pages: 5362-5375, ISSN: 1535-3893
Dona AC, Jimenez B, Schaefer H, et al., 2014, Precision High-Throughput Proton NMR Spectroscopy of Human Urine, Serum, and Plasma for Large-Scale Metabolic Phenotyping, ANALYTICAL CHEMISTRY, Vol: 86, Pages: 9887-9894, ISSN: 0003-2700
Ladep NG, Dona AC, Lewis MR, et al., 2014, Discovery and Validation of Urinary Metabotypes for the Diagnosis of Hepatocellular Carcinoma in West Africans, HEPATOLOGY, Vol: 60, Pages: 1291-1301, ISSN: 0270-9139
Lees H, Swann J, Poucher SM, et al., 2014, Age and Microenvironment Outweigh Genetic Influence on the Zucker Rat Microbiome, PLOS One, Vol: 9, ISSN: 1932-6203
ArticleAuthorsMetricsCommentsRelated ContentAbstractIntroductionMethodsResultsDiscussionConclusionsSupporting InformationAuthor ContributionsReferencesReader Comments (0)Media Coverage (0)FiguresAbstractAnimal models are invaluable tools which allow us to investigate the microbiome-host dialogue. However, experimental design introduces biases in the data that we collect, also potentially leading to biased conclusions. With obesity at pandemic levels animal models of this disease have been developed; we investigated the role of experimental design on one such rodent model. We used 454 pyrosequencing to profile the faecal bacteria of obese (n = 6) and lean (homozygous n = 6; heterozygous n = 6) Zucker rats over a 10 week period, maintained in mixed-genotype cages, to further understand the relationships between the composition of the intestinal bacteria and age, obesity progression, genetic background and cage environment. Phylogenetic and taxon-based univariate and multivariate analyses (non-metric multidimensional scaling, principal component analysis) showed that age was the most significant source of variation in the composition of the faecal microbiota. Second to this, cage environment was found to clearly impact the composition of the faecal microbiota, with samples from animals from within the same cage showing high community structure concordance, but large differences seen between cages. Importantly, the genetically induced obese phenotype was not found to impact the faecal bacterial profiles. These findings demonstrate that the age and local environmental cage variables were driving the composition of the faecal bacteria and were more deterministically important than the host genotype. These findings have major implications for understanding the significance of functional metagenomic data in experimental studies and beg the question; what is being measured in animal experiments in which different strains are housed separately, nature or nurture?
Xie G, Ma X, Zhao A, et al., 2014, The Metabolite Profiles of the Obese Population Are Gender-Dependent, JOURNAL OF PROTEOME RESEARCH, Vol: 13, Pages: 4062-4073, ISSN: 1535-3893
Venkatesh M, Mukherjee S, Wang H, et al., 2014, Symbiotic Bacterial Metabolites Regulate Gastrointestinal Barrier Function via the Xenobiotic Sensor PXR and Toll-like Receptor 4, IMMUNITY, Vol: 41, Pages: 296-310, ISSN: 1074-7613
Lindon JC, Nicholson JK, 2014, The emergent role of metabolic phenotyping in dynamic patient stratification, EXPERT OPINION ON DRUG METABOLISM & TOXICOLOGY, Vol: 10, Pages: 915-919, ISSN: 1742-5255
Sarafian MH, Gaudin M, Lewis MR, et al., 2014, Objective Set of Criteria for Optimization of Sample Preparation Procedures for Ultra-High Throughput Untargeted Blood Plasma Lipid Profiling by Ultra Performance Liquid Chromatography-Mass Spectrometry, ANALYTICAL CHEMISTRY, Vol: 86, Pages: 5766-5774, ISSN: 0003-2700
Martin FP, BOULANGE CL, MONTOLIU ROURA I, et al., 2014, Isovalerylglycine as biomarker for the predisposition for weight gain and obesity, WO2014086605
The present invention relates generally to the field of nutrition and health. In particular, the present invention relates to a new biomarker, its use and a method that allows it to diagnose the likelihood to resist diet induced weight gain, and/or to be susceptible to a diet induced weight gain. For example, the biomarker may be isovalerylglycine.
MARTIN FP, Boulange CL, Montoliu Roura I, et al., 2014, Hexanoylglycine as biomarker for the predisposition for weight gain and obesity, WO 2014/086603
The present invention relates generally to the field of nutrition and health. In particular, the present invention relates to a new biomarker, its use and a method that allows it to diagnose the likelihood to resist diet induced weight gain, and/or to be susceptible to a diet induced weight gain. For example, the biomarker may be hexanoylglycine.
Martin FP, Boulange CL, Montoliu Roura I, et al., 2014, Trimethylamine-N-oxide as biomarker for the predisposition for weight gain and obesity, WO2014086604
The present invention relates generally to the field of nutrition and health. In particular, the present invention relates to a new biomarker, its use and a nnethod that allows it to diagnose the likelihood to resist diet induced weight gain, and/or to be susceptible to a diet induced weight gain. For example, the biomarker may be trimethylamine-N-oxide.
Zou X, Holmes E, Nicholson JK, et al., 2014, Statistical HOmogeneous Cluster SpectroscopY (SHOCSY): An Optimized Statistical Approach for Clustering of H-1 NMR Spectral Data to Reduce Interference and Enhance Robust Biomarkers Selection, ANALYTICAL CHEMISTRY, Vol: 86, Pages: 5308-5315, ISSN: 0003-2700
Mirnezami R, Jimenez B, Li JV, et al., 2014, Rapid Diagnosis and Staging of Colorectal Cancer via High-Resolution Magic Angle Spinning Nuclear Magnetic Resonance (HR-MAS NMR) Spectroscopy of Intact Tissue Biopsies, ANNALS OF SURGERY, Vol: 259, Pages: 1138-1149, ISSN: 0003-4932
Chandiramani M, Lee Y, Kindinger L, et al., 2014, 8.6 The evolution of the vaginal microbiome throughout uncomplicated pregnancy in a UK population., Pages: A12-A13
The vaginal microbiome plays an important role in maintaining reproductive health throughout pregnancy. Despite the presence of an 'abnormal' vaginal microbial community being associated with an increased risk of preterm birth, interventional trials of antibiotics have failed to demonstrate significant benefit, which is likely due to a poor understanding of the vaginal microbiome in pregnancy. We sought to characterise the vaginal microbiome in uncomplicated pregnancies in a UK-based cohort.
Kinross J, Muirhead LJ, Mirnezami R, et al., 2014, Microbiome-Metabonome Linked Analysis of Ascending Colon Cancer by 1HNMR MAS Spectrometry and 16S rRNA Gene Analysis (Metataxonomics), 55th Annual Meeting of the Society-for-Surgery-of-the-Alimentary-Tract (SSAT) / Digestive Disease Week (DDW), Publisher: W B SAUNDERS CO-ELSEVIER INC, Pages: S688-S688, ISSN: 0016-5085
Kinross J, Li J, Lahti L, et al., 2014, A High Fat Lower Fiber Dietary Intervention Perturbs the Urinary Metabonome and Gut Microbial Co-Metabolic Processes in a Population of African and African Americans, 55th Annual Meeting of the Society-for-Surgery-of-the-Alimentary-Tract (SSAT) / Digestive Disease Week (DDW), Publisher: W B SAUNDERS CO-ELSEVIER INC, Pages: S543-S544, ISSN: 0016-5085
Kinross J, Li JV, Muirhead LJ, et al., 2014, Nutritional modulation of the metabonome: applications of metabolic phenotyping in translational nutritional research, CURRENT OPINION IN GASTROENTEROLOGY, Vol: 30, Pages: 196-207, ISSN: 0267-1379
MacIntyre DA, Lee YS, Marchesi J, et al., 2014, Preterm Premature Rupture of Membranes (PPROM) Is Associated with Disparate Vaginal Microbiomes That Are Correlated with Specific Urinary Metabolic Profiles, 61st Annual Scientific Meeting of the Society-for-Gynecologic-Investigation (SGI), Publisher: SAGE PUBLICATIONS INC, Pages: 246A-246A, ISSN: 1933-7191
Ashrafian H, Li J, Spagou K, et al., 2014, Bariatric surgery modulates circulating and cardiac metabolites, Journal of Proteome Research, Vol: 13, Pages: 570-580, ISSN: 1535-3893
Bariatric procedures such as the Roux-en-Y gastric bypass (RYGB) operation offer profound metabolic enhancement in addition to their well-recognized weight loss effects. They are associated with significant reduction in cardiovascular disease risk and mortality, which suggests a surgical modification on cardiac metabolism. Metabolic phenotyping of the cardiac tissue and plasma postsurgery may give insight into cardioprotective mechanisms. The aim of the study was to compare the metabolic profiles of plasma and heart tissue extracts from RYGB- and sham-operated Wistar rats to identify the systemic and cardiac signature of metabolic surgery. A total of 27 male Wistar rats were housed individually for a week and subsequently underwent RYGB (n = 13) or sham (n = 14) operation. At week 8 postoperation, a total of 27 plasma samples and 16 heart tissue samples (8 RYGB; 8 Sham) were collected from animals and analyzed using 1H nuclear magnetic resonance (NMR) spectroscopy and ultra performance liquid chromatography (UPLC-MS) to characterize the global metabolite perturbation induced by RYGB operation. Plasma bile acids, phosphocholines, amino acids, energy-related metabolites, nucleosides and amine metabolites, and cardiac glycogen and amino acids were found to be altered in the RYGB operated group. Correlation networks were used to identify metabolite association. The metabolic phenotype of this bariatric surgical model inferred systematic change in both myocardial and systemic activity post surgery. The altered metabolic profile following bariatric surgery reflects an enhancement of cardiac energy metabolism through TCA cycle intermediates, cardiorenal protective activity, and biochemical caloric restriction. These surgically induced metabolic shifts identify some of the potential mechanisms that contribute toward bariatric cardioprotection through gut microbiota ecological fluxes and an enterocardiac axis to shield against metabolic syndrome of cardiac dysfunction.
Mirnezami R, Spagou K, Vorkas PA, et al., 2014, Chemical mapping of the colorectal cancer microenvironment via MALDI imaging mass spectrometry (MALDI-MSI) reveals novel cancer-associated field effects, MOLECULAR ONCOLOGY, Vol: 8, Pages: 39-49, ISSN: 1878-0261
Veselkov KA, Mirnezami R, Strittmatter N, et al., 2014, Chemo-informatic strategy for imaging mass spectrometry-based hyperspectral profiling of lipid signatures in colorectal cancer, Proceedings of the National Academy of Sciences of the United States of America, Vol: 111, Pages: 1216-1221, ISSN: 0027-8424
Mass spectrometry imaging (MSI) provides the opportunity toinvestigate tumor biology from an entirely novel biochemicalperspective and could lead to the identification of a new pool ofcancer biomarkers. Effective clinical translation of histology-drivenMSI in systems oncology requires precise colocalization of morphologicaland biochemical features as well as advanced methodsfor data treatment and interrogation. Currently proposed MSIworkflows are subject to several limitations, including nonoptimizedraw data preprocessing, imprecise image coregistration,and limited pattern recognition capabilities. Here we outline acomprehensive strategy for histology-driven MSI, using desorptionelectrospray ionization that covers (i) optimized data preprocessingfor improved information recovery; (ii) precise imagecoregistration; and (iii) efficient extraction of tissue-specific molecularion signatures for enhanced biochemical distinction of differenttissue types. The proposed workflow has been used to investigateregion-specific lipid signatures in colorectal cancer tissue. Uniquelipid patterns were observed using this approach according totissue type, and a tissue recognition system using multivariatemolecular ion patterns allowed highly accurate (>98%) identificationof pixels according to morphology (cancer, healthy mucosa,smooth muscle, and microvasculature). This strategy offers uniqueinsights into tumor microenvironmental biochemistry and shouldfacilitate compilation of a large-scale tissue morphology-specificMSI spectral database with which to pursue next-generation, fullyautomated histological approaches.
Klootwijk ED, Reichold M, Helip-Wooley A, et al., 2014, Mistargeting of Peroxisomal EHHADH and Inherited Renal Fanconi's Syndrome, NEW ENGLAND JOURNAL OF MEDICINE, Vol: 370, Pages: 129-138, ISSN: 0028-4793
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