PubMed

Related Articles Crosstalk between branched chain amino acids and hepatic mitochondria is compromised in nonalcoholic fatty liver disease. Am J Physiol Endocrinol Metab. 2015 Jun 9;:ajpendo.00161.2015 Authors: Sunny NE, Kalavalapalli S, Bril F, Garrett TJ, Nautiyal M, Mathew JT, Williams CM, Cusi K Abstract Elevated plasma branched chain amino acids (BCAA) in the setting of insulin resistance have been relevant in predicting type 2 diabetes mellitus (T2DM) onset, but their role in the etiology of hepatic insulin resistance remains uncertain. We determined the link between BCAA and dysfunctional hepatic tri-carboxylic acid (TCA) cycle, which is a central feature of hepatic insulin resistance and nonalcoholic fatty liver disease (NAFLD). Plasma metabolites under basal fasting and euglycemic hyperinsulinemic clamps (insulin stimulation) were measured in 94 human subjects with varying degrees of insulin sensitivity, to identify their relationships with insulin resistance. Further, the impact of elevated BCAA on hepatic TCA cycle was determined in a diet induced mouse model of NAFLD, utilizing targeted metabolomics and nuclear magnetic resonance (NMR) based metabolic flux analysis. Insulin stimulation revealed robust relationships between human plasma BCAA and indices of insulin resistance, indicating chronic metabolic overload from BCAA. Human plasma BCAA and long chain acylcarnitines also showed a positive correlation, suggesting modulation of mitochondrial metabolism by BCAA. Concurrently, mice with NAFLD failed to optimally induce hepatic mTORC1, plasma ketones and hepatic long chain acylcarnitines, following acute elevation of plasma BCAA. Furthermore, elevated BCAA failed to induce multiple fluxes through hepatic TCA cycle in mice with NAFLD. Our data suggest that BCAA are essential to mediate efficient channeling of carbon substrates for oxidation through mitochondrial TCA cycle. Impairment of BCAA-mediated up-regulation of TCA cycle could be a significant contributor to mitochondrial dysfunction in NAFLD. PMID: 26058864 [PubMed - as supplied by publisher]

Related Articles Metabolite profiling in plasma and tissues of ob/ob and db/db mice identifies novel markers of obesity and type 2 diabetes. Diabetologia. 2015 Jun 10; Authors: Giesbertz P, Padberg I, Rein D, Ecker J, Höfle AS, Spanier B, Daniel H Abstract AIMS/HYPOTHESIS: Metabolomics approaches in humans have identified around 40 plasma metabolites associated with insulin resistance (IR) and type 2 diabetes, which often coincide with those for obesity. We aimed to separate diabetes-associated from obesity-associated metabolite alterations in plasma and study the impact of metabolically important tissues on plasma metabolite concentrations. METHODS: Two obese mouse models were studied; one exclusively with obesity (ob/ob) and another with type 2 diabetes (db/db). Both models have impaired leptin signalling as a cause for obesity, but the different genetic backgrounds determine the susceptibility to diabetes. In these mice, we profiled plasma, liver, skeletal muscle and adipose tissue via semi-quantitative GC-MS and quantitative liquid chromatography (LC)-MS/MS for a wide range of metabolites. RESULTS: Metabolite profiling identified 24 metabolites specifically associated with diabetes but not with obesity. Among these are known markers such as 1,5-anhydro-D-sorbitol, 3-hydroxybutyrate and the recently reported marker glyoxylate. New metabolites in the diabetic model were lysine, O-phosphotyrosine and branched-chain fatty acids. We also identified 33 metabolites that were similarly altered in both models, represented by branched-chain amino acids (BCAA) as well as glycine, serine, trans-4-hydroxyproline, and various lipid species and derivatives. Correlation analyses showed stronger associations for plasma amino acids with adipose tissue metabolites in db/db mice compared with ob/ob mice, suggesting a prominent contribution of adipose tissue to changes in plasma in a diabetic state. CONCLUSIONS/INTERPRETATION: By studying mice with metabolite signatures that resemble obesity and diabetes in humans, we have found new metabolite entities for validation in appropriate human cohorts and revealed their possible tissue of origin. PMID: 26058503 [PubMed - as supplied by publisher]

Related Articles Glucose and glycerol concentrations and their tracer enrichment measurements using liquid chromatography tandem mass spectrometry. J Mass Spectrom. 2014 Oct;49(10):980-8 Authors: Bornø A, Foged L, van Hall G Abstract The present study describes a new liquid chromatography tandem mass spectrometry method for high-throughput quantification of glucose and glycerol in human plasma using stable isotopically labeled internal standards and is suitable for simultaneous measurements of glucose and glycerol enrichments in connection to in vivo metabolic studies investigating glucose turnover and lipolytic rate. Moreover, in order to keep up with this new fast analysis, simple derivatization procedures have been developed. Prior to analysis, glucose and glycerol were derivatized using benzoyl chloride in order to form benzoylated derivatives via new simplified fast procedures. For glucose, two internal standards were evaluated, [U-(13) C(6)]glucose and [U-(13) C(6), D(7)]glucose, and for glycerol, [U-(13) C(3), D(8)]glycerol was used. The method was validated by means of calibration curves, quality control samples, and plasma samples spiked with [6,6-D(2)]glucose, [U-(13) C(6)]glucose, and [1,1,2,3,3-D(5)]glycerol in order to test accuracy, precision, and recovery of the method. Moreover, post preparative and freeze-thaw sample stability were tested. The correlation of calibration curves for the glucose concentration were r(2) = 0.9998 for [U-(13) C(6)]glucose and r(2) = 0.9996 for [U-(13) C(6), D(7)]glucose, and r(2) = 0.9995 for the glycerol concentration. Interday accuracy for glucose using [U-(13) C(6)]glucose and glycerol determined in spiked plasma were respectively 103.5% and 106.0%, and the coefficients of variation were 2.0% and 9.7%, respectively. After derivatization, plasma samples were stable for at least 14 days. In conclusion, we have developed and validated a novel, accurate, and sensitive high-throughput liquid chromatography tandem mass spectrometry method for simultaneous determination of glucose and glycerol concentrations and enrichment of infused tracers most commonly used in human metabolic kinetic studies. PMID: 25303387 [PubMed - indexed for MEDLINE]

Related Articles Combined mass spectrometry-based metabolite profiling of different pigmented rice (Oryza sativa L.) seeds and correlation with antioxidant activities. Molecules. 2014;19(10):15673-86 Authors: Kim GR, Jung ES, Lee S, Lim SH, Ha SH, Lee CH Abstract Nine varieties of pigmented rice (Oryza sativa L.) seeds that were black, red, or white were used to perform metabolite profiling by using ultra-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry (UPLC-Q-TOF-MS) and gas chromatography (GC) TOF-MS, to measure antioxidant activities. Clear grouping patterns determined by the color of the rice seeds were identified in principle component analysis (PCA) derived from UPLC-Q-TOF-MS. Cyanidin-3-glucoside, peonidin-3-glucoside, proanthocyanidin dimer, proanthocyanidin trimer, apigenin-6-C-glugosyl-8-C-arabiboside, tricin-O-rhamnoside-O-hexoside, and lipids were identified as significantly different secondary metabolites. In PCA score plots derived from GC-TOF-MS, Jakwangdo (JKD) and Ilpoom (IP) species were discriminated from the other rice seeds by PC1 and PC2. Valine, phenylalanine, adenosine, pyruvate, nicotinic acid, succinic acid, maleic acid, malonic acid, gluconic acid, xylose, fructose, glucose, maltose, and myo-inositol were significantly different primary metabolites in JKD species, while GABA, asparagine, xylitol, and sucrose were significantly distributed in IP species. Analysis of antioxidant activities revealed that black and red rice seeds had higher activity than white rice seeds. Cyanidin-3-glucoside, peonidin-3-glucoside, proanthocyanidin dimers, proanthocyanidin trimers, and catechin were highly correlated with antioxidant activities, and were more plentiful in black and red rice seeds. These results are expected to provide valuable information that could help improve and develop rice-breeding techniques. PMID: 25268721 [PubMed - indexed for MEDLINE]

Related Articles Novel genetic associations with serum level metabolites identified by phenotype set enrichment analyses. Hum Mol Genet. 2014 Nov 1;23(21):5847-57 Authors: Ried JS, Shin SY, Krumsiek J, Illig T, Theis FJ, Spector TD, Adamski J, Wichmann HE, Strauch K, Soranzo N, Suhre K, Gieger C Abstract Availability of standardized metabolite panels and genome-wide single-nucleotide polymorphism data endorse the comprehensive analysis of gene-metabolite association. Currently, many studies use genome-wide association analysis to investigate the genetic effects on single metabolites (mGWAS) separately. Such studies have identified several loci that are associated not only with one but with multiple metabolites, facilitated by the fact that metabolite panels often include metabolites of the same or related pathways. Strategies that analyse several phenotypes in a combined way were shown to be able to detect additional genetic loci. One of those methods is the phenotype set enrichment analysis (PSEA) that tests sets of metabolites for enrichment at genes. Here we applied PSEA on two different panels of serum metabolites together with genome-wide data. All analyses were performed as a two-step identification-validation approach, using data from the population-based KORA cohort and the TwinsUK study. In addition to confirming genes that were already known from mGWAS, we were able to identify and validate 12 new genes. Knowledge about gene function was supported by the enriched metabolite sets. For loci with unknown gene functions, the results suggest a function that is interrelated with the metabolites, and hint at the underlying pathways. PMID: 24927737 [PubMed - indexed for MEDLINE]

Related Articles Tuning intracellular homeostasis of human uroporphyrinogen III synthase by enzyme engineering at a single hotspot of congenital erythropoietic porphyria. Hum Mol Genet. 2014 Nov 1;23(21):5805-13 Authors: ben Bdira F, González E, Pluta P, Laín A, Sanz-Parra A, Falcon-Perez JM, Millet O Abstract Congenital erythropoietic porphyria (CEP) results from a deficiency in uroporphyrinogen III synthase enzyme (UROIIIS) activity that ultimately stems from deleterious mutations in the uroS gene. C73 is a hotspot for these mutations and a C73R substitution, which drastically reduces the enzyme activity and stability, is found in almost one-third of all reported CEP cases. Here, we have studied the structural basis, by which mutations in this hotspot lead to UROIIIS destabilization. First, a strong interdependency is observed between the volume of the side chain at position 73 and the folded protein. Moreover, there is a correlation between the in vitro half-life of the mutated proteins and their expression levels in eukaryotic cell lines. Molecular modelling was used to rationalize the results, showing that the mutation site is coupled to the hinge region separating the two domains. Namely, mutations at position 73 modulate the inter-domain closure and ultimately affect protein stability. By incorporating residues capable of interacting with R73 to stabilize the hinge region, catalytic activity was fully restored and a moderate increase in the kinetic stability of the enzyme was observed. These results provide an unprecedented rationale for a destabilizing missense mutation and pave the way for the effective design of molecular chaperones as a therapy against CEP. PMID: 24925316 [PubMed - indexed for MEDLINE]

Related Articles The future of the laboratory information system - what are the requirements for a powerful system for a laboratory data management? Clin Chem Lab Med. 2014 Nov;52(11):e225-30 Authors: Kammergruber R, Robold S, Karliç J, Durner J PMID: 24897404 [PubMed - indexed for MEDLINE]

Metabolism alteration in follicular niche: The nexus between intermediary metabolism, mitochondrial function, and classic polycystic ovary syndrome. Free Radic Biol Med. 2015 Jun 6; Authors: Zhao H, Zhao Y, Li T, Li M, Li J, Li R, Liu P, Yu Y, Qiao J Abstract Classic polycystic ovary syndrome (PCOS) is a high-risk phenotype accompanied by increased risks of reproductive and metabolic abnormalities; however, the local metabolism characteristics of the ovaries and their effects on germ cell development are unclear. The present study used targeted metabolomics to detect alterations in the intermediate metabolites of follicular fluid from classic PCOS patients, and the results indicated hyperandrogenism, but not obesity induced the changed intermediate metabolites in classic PCOS patients. Regarding the direct contact, we identified mitochondrial function, redox potential and oxidative stress in cumulus cells which werenecessary to support oocyte growth before fertilization, and suggested dysfunction of mitochondria, imbalanced redox potential and increased oxidative stress in cumulus cells of classic PCOS patients. Follicular fluid intermediary metabolic profiles provide signatures of classic PCOS ovary local metabolism and establish close link with mitochondria dyfunction of cumulus cells and highlighting the role of metabolic signal and mitochondrial crosstalk involved in the pathogenesis of classic PCOS. PMID: 26057937 [PubMed - as supplied by publisher]

Metabolome strategy against Edwardsiella tarda infection through glucose-enhanced metabolic modulation in tilapias. Fish Shellfish Immunol. 2015 Jun 6; Authors: Peng B, Ma YM, Zhang JY, Li H Abstract Edwardsiella tarda causes fish disease and great economic loss. However, metabolic strategy against the pathogen remains unexplored. In the present study, GC-MS based metabolomics was used to investigate the metabolic profile from tilapias infected by sublethal dose of E. tarda. The metabolic differences between the dying group and survival group allow the identification of key pathways and crucial metabolites during infections. More importantly, those metabolites may modulate the survival-related metabolome to enhance the anti-infective ability. Our data showed that tilapias generated two different strategies, survival-metabolome and death-metabolome, to encounter EIB202 infection, leading to differential outputs of the survival and dying. Glucose was the most crucial biomarker, which was upregulated and downregulated in the survival and dying groups, respectively. Exogenous glucose by injection or oral administration enhanced hosts' ability against EIB202 infection and increased the chances of survival. These findings highlight that host mounts the metabolic strategy to cope with bacterial infection, from which crucial biomarkers may be identified to enhance the metabolic strategy. PMID: 26057462 [PubMed - as supplied by publisher]

Related Articles Tissue lipid metabolism and hepatic metabolomic profiling in response to supplementation of fermented cottonseed meal in the diets of broiler chickens. J Zhejiang Univ Sci B. 2015 Jun;16(6):447-55 Authors: Nie CX, Zhang WJ, Wang YQ, Liu YF, Ge WX, Liu JC Abstract This study investigated the effects of fermented cottonseed meal (FCSM) on lipid metabolites, lipid metabolism-related gene expression in liver tissues and abdominal adipose tissues, and hepatic metabolomic profiling in broiler chickens. One hundred and eighty 21-d-old broiler chickens were randomly divided into three diet groups with six replicates of 10 birds in each group. The three diets consisted of a control diet supplemented with unfermented cottonseed meal, an experimental diet of cottonseed meal fermented by Candida tropicalis, and a second experimental diet of cottonseed meal fermented by C. tropicalis plus Saccharomyces cerevisae. The results showed that FCSM intake significantly decreased the levels of abdominal fat and hepatic triglycerides (P<0.05 for both). Dietary FCSM supplementation down-regulated the mRNA expression of fatty acid synthase and acetyl CoA carboxylase in liver tissues and the lipoprotein lipase expression in abdominal fat tissues (P<0.05 for both). FCSM intake resulted in significant metabolic changes of multiple pathways in the liver involving the tricarboxylic acid cycle, synthesis of fatty acids, and the metabolism of glycerolipid and amino acids. These findings indicated that FCSM regulated lipid metabolism by increasing or decreasing the expression of the lipid-related gene and by altering multiple endogenous metabolites. Lipid metabolism regulation is a complex process, this discovery provided new essential information about the effects of FCSM diets in broiler chickens and demonstrated the great potential of nutrimetabolomics in researching complex nutrients added to animal diets. PMID: 26055906 [PubMed - in process]

Related Articles Nephron Toxicity Profiling via Untargeted Metabolome Analysis Employing a High-Performance Liquid Chromatography-Mass Spectrometry-Based Experimental and Computational Pipeline. J Biol Chem. 2015 Jun 8; Authors: Ranninger C, Rurik M, Limonciel A, Ruzek S, Reischl R, Wilmes A, Jennings P, Hewitt P, Dekant W, Kohlbacher O, Huber CG Abstract Untargeted metabolomics has the potential to improve the predictivity of in vitro toxicity models and therefore may aid the replacement of expensive and laborious animal models. Here we describe a long-term repeat dose nephrotoxicity study conducted on the human renal proximal tubular epithelial cell line, RPTEC/TERT1, treated with 10 μmol.L-1 and 35 μmol.L-1 of chloroacetaldehyde - a metabolite of the anti-cancer drug ifosfamide. Our study outlines the establishment of an automated and easy to use untargeted metabolomics workflow for HPLC-HRMS data. Automated data analysis workflows based on open-source software (OpenMS, KNIME) enabled a comprehensive and reproducible analysis of the complex and voluminous metabolomics data produced by the profiling approach. Time- and concentration dependent responses were clearly evident in the metabolomic profiles. In order to obtain a more comprehensive picture of the mode of action, transcriptomics and proteomics data were also integrated. For toxicity profiling of chloroacetaldehyde, 428 and 317 metabolite features were detectable in positive and negative mode, respectively, after stringent removal of chemical noise and unstable signals. Changes upon treatment were explored using principal component analysis (PCA) and statistically significant differences were identified using linear models (LIMMA). The analysis revealed toxic effects only for the treatment with 35 μmol.L-1 for 3 and 14 days. The most regulated metabolites were glutathione and metabolites related to the oxidative stress response of the cells. These findings are corroborated by proteomics and transcriptomics data, which show, amongst others, an activation of the Nrf2 and ATF4 pathways. PMID: 26055719 [PubMed - as supplied by publisher]

Related Articles Cardiac metabolomics and autopsy in a patient with early diffuse systemic sclerosis presenting with dyspnea: a case report. J Med Case Rep. 2015 Jun 10;9(1):136 Authors: Frech TM, Revelo MP, Ryan JJ, Shah AA, Gordon J, Domsic R, Hant F, Assassi S, Shanmugam VK, Hinchcliff M, Steen V, Khanna D, Bernstein EJ, Cox J, Luem N, Drakos S Abstract INTRODUCTION: Diffuse systemic sclerosis is associated with high mortality; however, the pathogenesis of cardiac death in these patients is not clear. CASE PRESENTATION: A 56-year-old Caucasian female patient presented with dyspnea and requested to donate her body to science in order to improve understanding of diffuse systemic sclerosis pathogenesis. She had extensive testing for dyspnea including pulmonary function tests, an echocardiogram, cardiac magnetic resonance imaging, and right heart catheterization to characterize her condition. Her case highlights the morbidity seen in this disease, including the presence of extensive skin thickening, digital ulcerations, and scleroderma renal crisis. CONCLUSION: In this case report, we present the finding of cardiac tissue metabolomics, which may indicate a problem with vasodilation as a contributor to cardiac death in diffuse systemic sclerosis. The use of autopsy and tissue metabolomics in rare disease may help clarify disease pathogenesis. PMID: 26055398 [PubMed - as supplied by publisher]

Related Articles Delving deeper into technological innovations to understand differences in rice quality. Rice (N Y). 2015 Dec;8(1):43 Authors: Calingacion M, Fang L, Quiatchon-Baeza L, Mumm R, Riedel A, Hall RD, Fitzgerald M Abstract Increasing demand for better quality rice varieties, which are also more suited to growth under sub-optimal cultivation conditions, is driving innovation in rice research. Here we have used a multi-disciplinary approach, involving SNP-based genotyping together with phenotyping based on yield analysis, metabolomic analysis of grain volatiles, and sensory panel analysis to determine differences between two contrasting rice varieties, Apo and IR64. Plants were grown under standard and drought-induced conditions. Results revealed important differences between the volatile profiles of the two rice varieties and we relate these differences to those perceived by the sensory panel. Apo, which is the more drought tolerant variety, was less affected by the drought condition concerning both sensory profile and yield; IR64, which has higher quality but is drought sensitive, showed greater differences in these characteristics in response to the two growth conditions. Metabolomics analyses using GCxGC-MS, followed by multivariate statistical analyses of the data, revealed a number of discriminatory compounds between the varieties, but also effects of the difference in cultivation conditions. Results indicate the complexity of rice volatile profile, even of non-aromatic varieties, and how metabolomics can be used to help link changes in aroma profile with the sensory phenotype. Our outcomes also suggest valuable multi-disciplinary approaches which can be used to help define the aroma profile in rice, and its underlying genetic background, in order to support breeders in the generation of improved rice varieties combining high yield with high quality, and tolerance of both these traits to climate change. PMID: 26054242 [PubMed]

Related Articles Harnessing the heart of big data. Circ Res. 2015 Mar 27;116(7):1115-9 Authors: Scruggs SB, Watson K, Su AI, Hermjakob H, Yates JR, Lindsey ML, Ping P PMID: 25814682 [PubMed - indexed for MEDLINE]

Related Articles Surveillance for lower airway pathogens in mechanically ventilated patients by metabolomic analysis of exhaled breath: a case-control study. Thorax. 2015 Apr;70(4):320-5 Authors: Fowler SJ, Basanta-Sanchez M, Xu Y, Goodacre R, Dark PM Abstract BACKGROUND: Healthcare associated infections, including ventilator associated pneumonia, are difficult to diagnose and treat, and are associated with significant morbidity, mortality and cost. We aimed to demonstrate proof of concept that breath volatile profiles were associated with the presence of clinically relevant pathogens in the lower respiratory tract. METHODS: Patients with sterile brain injury requiring intubation and ventilation on the intensive care unit were eligible for inclusion. Serial clinical and breath data were obtained three times a week, from admission up to a maximum of 10 days. Bronchial lavage for semiquantitative culture was collected immediately prior to breath sampling. Breath samples were collected in triplicate for off-line analysis by thermal-desorption/gas chromatography/time-of-flight mass spectrometry. Breath data were recorded as retention time/mass ion pairs, and analysed (pathogen present vs absent) by ANOVA-mean centre principal component analysis. RESULTS: Samples were collected from 46 patients (mean (SD) age 49 (19) years; 27 male). The dominant factors affecting breath sample analysis were the individual breath profile and duration of intubation. When these were taken into account, clear separation was seen between breath profiles at each time point by the presence/absence of pathogens. Loadings plots identified consistent metabolite peaks contributing to this separation at each time point. CONCLUSIONS: Breath volatile analysis is able to classify breath profiles of patients with and without significant pathogen load in the lower respiratory tract. If validated in independent cohorts, these findings could lead to development of rapid non-invasive point-of-care surveillance systems and diagnostics for lower respiratory tract infection in the intensive care unit. PMID: 25661115 [PubMed - indexed for MEDLINE]

Related Articles Successful treatment of Cronkhite-Canada syndrome using anti-tumor necrosis factor antibody therapy. Endoscopy. 2014;46 Suppl 1 UCTN:E476-7 Authors: Watanabe D, Ooi M, Hoshi N, Kohashi M, Yoshie T, Ikehara N, Yoshida M, Yanagita E, Yamasaki T, Itoh T, Azuma T PMID: 25314205 [PubMed - indexed for MEDLINE]

Related Articles [Analyzing the inhibition of vitamin B12 to dexamethasone-induced palatognathous mouse using 1H-nuclear magnetic resonance based metabonomics method]. Hua Xi Kou Qiang Yi Xue Za Zhi. 2010 Jun;28(3):311-4 Authors: Wu XH, Huang H, Xu B, Zhou JL, Kong XL, Shi B, Huang J, Li W Abstract OBJECTIVE: Metabonomic analysis has been increasingly used to monitor metabolic abnormalities in cells and their micro-environment in order to detect the biomarkers recently. This study evaluated the feasibility of applying 1H-nuclear magnetic resonance (1H-NMR) based metabonomic method to detect the differences of the early development of cleft palate in the plasma from control group and experimental group. METHODS: Pregnant mice (inbred C57BL/6J strain) with vitamin B12 injected only were assigned as the control group, pregnant mice with excessive Dex, injected after vitamin B12 as the experimental group, each group includes 12 mice. And the effect of B12 to rate of cleft palate was observed. The technology of nuclear magnetic resonance (NMR) was used to detect the endogenous small molecule metabolites. Finally, changes of metabolites ingredients were ascertained by using the method of principal component analysis (PCA). RESULTS: There was significant difference in PCA scores plot between the two groups according to whether cleft palate occurred. CONCLUSION: The 1H-NMR based metabonomic approach might be used as a feasible and efficient method for a deep exploration of the pathogenesis of cleft lip and palate and an early exploration of the mechanism of vitamin B12. PMID: 20635665 [PubMed - indexed for MEDLINE]

Future perspectives in Orbitrap™ high resolution mass spectrometry in food analysis - a review. Food Addit Contam Part A Chem Anal Control Expo Risk Assess. 2015 Jun 8; Authors: Senyuva HZ, Gokmen V, Sarikaya EA Abstract We have conducted a literature search from 2007-2014 to identify publications where principally LC-Orbitrap™ high resolution mass spectrometry (HRMS) has been employed in food analysis. Of a total of 212 relevant references, only 22 papers were from the years 2007-2010, but in subsequent years there has been a steady growth in publications with 38 to 55 relevant papers being published each year from 2011-2014. In the food safety area over 50% of the published papers were equally divided between pesticides, veterinary drug residues and natural toxins (including mycotoxins) focussed primarily on multi-analyte target analysis. LC- Orbitrap™ HRMS was also found to be increasingly important for the analysis of bioactive substances, principally phenolic compounds in foods. A number of studies reported for the first time the identification of new fungal metabolites, predominantly various conjugated forms of known mycotoxins. Novel process contaminants were also identified by LC-Orbitrap™ HRMS, as were various substances used for food adulteration and bioactive substances in herbal products and dietary supplements. Untargeted analysis is seen as a major future trend where HRMS plays a significant role. Retrospective analysis of scanned HR mass spectra in conjunction with relevant databases can provide new insights. Metabolomics is also being increasingly used where foods are being profiled through fingerprinting using HRMS. All evidence points towards future growth in the number of applications of HRMS in food safety and quality, as the power of this technique gains wider recognition. PMID: 26053336 [PubMed - as supplied by publisher]

ONION: Functional Approach for Integration of Lipidomics and Transcriptomics Data. PLoS One. 2015;10(6):e0128854 Authors: Piwowar M, Jurkowski W Abstract To date, the massive quantity of data generated by high-throughput techniques has not yet met bioinformatics treatment required to make full use of it. This is partially due to a mismatch in experimental and analytical study design but primarily due to a lack of adequate analytical approaches. When integrating multiple data types e.g. transcriptomics and metabolomics, multidimensional statistical methods are currently the techniques of choice. Typical statistical approaches, such as canonical correlation analysis (CCA), that are applied to find associations between metabolites and genes are failing due to small numbers of observations (e.g. conditions, diet etc.) in comparison to data size (number of genes, metabolites). Modifications designed to cope with this issue are not ideal due to the need to add simulated data resulting in a lack of p-value computation or by pruning of variables hence losing potentially valid information. Instead, our approach makes use of verified or putative molecular interactions or functional association to guide analysis. The workflow includes dividing of data sets to reach the expected data structure, statistical analysis within groups and interpretation of results. By applying pathway and network analysis, data obtained by various platforms are grouped with moderate stringency to avoid functional bias. As a consequence CCA and other multivariate models can be applied to calculate robust statistics and provide easy to interpret associations between metabolites and genes to leverage understanding of metabolic response. Effective integration of lipidomics and transcriptomics is demonstrated on publically available murine nutrigenomics data sets. We are able to demonstrate that our approach improves detection of genes related to lipid metabolism, in comparison to applying statistics alone. This is measured by increased percentage of explained variance (95% vs. 75-80%) and by identifying new metabolite-gene associations related to lipid metabolism. PMID: 26053255 [PubMed - as supplied by publisher]

Resolution-enhanced 2D NMR of complex mixtures by non-uniform sampling. Magn Reson Chem. 2015 Jun 6; Authors: Le Guennec A, Dumez JN, Giraudeau P, Caldarelli S Abstract NMR is a powerful tool for the analysis of complex mixtures and the identification of individual components. Two-dimensional (2D) NMR potentially offers a wealth of information, but resolution is often sacrificed in order to contain experimental times. We explore the use of non-uniform sampling (NUS) to increase substantially the resolution of 2D NMR spectra of complex mixtures of small molecules, with no increase in experimental time. Two common pulse sequences for metabolomics applications are analysed, HSQC and TOCSY. Specific attention is paid to sensitivity in resolution-enhanced NUS spectra, using the signal-to-maximum-noise ratio as a metric. With a careful choice of sampling schedule and reconstruction algorithm, resolution in the (13) C dimension for HSQC is increased by a factor of at least 32, with no loss in sensitivity and no spurious peaks. For TOCSY, multiplets can be resolved in the indirect dimension in a reasonable experimental time. These properties should increase the usefulness of 2D NMR for metabolomics applications by, for example, increasing the chances of metabolite identification. Copyright © 2015 John Wiley & Sons, Ltd. PMID: 26053155 [PubMed - as supplied by publisher]