Metabolomics : Official journal of the Metabolomic Society最新文献

{"title":"Retinal metabolic events in preconditioning light stress as revealed by wide-spectrum targeted metabolomics.","authors":"Juan Manuel Chao de la Barca,&nbsp;Nuan-Ting Huang,&nbsp;Haihan Jiao,&nbsp;Lydie Tessier,&nbsp;Cédric Gadras,&nbsp;Gilles Simard,&nbsp;Riccardo Natoli,&nbsp;Guillaume Tcherkez,&nbsp;Pascal Reynier,&nbsp;Krisztina Valter","doi":"10.1007/s11306-016-1156-9","DOIUrl":"https://doi.org/10.1007/s11306-016-1156-9","url":null,"abstract":"<p><strong>Introduction: </strong>Light is the primary stimulus for vision, but may also cause damage to the retina. Pre-exposing the retina to sub-lethal amount of light (or preconditioning) improves chances for retinal cells to survive acute damaging light stress.</p><p><strong>Objectives: </strong>This study aims at exploring the changes in retinal metabolome after mild light stress and identifying mechanisms that may be involved in preconditioning.</p><p><strong>Methods: </strong>Retinas from 12 rats exposed to mild light stress (1000 lux × for 12 h) and 12 controls were collected one and seven days after light stress (LS). One retina was used for targeted metabolomics analysis using the Biocrates p180 kit while the fellow retina was used for histological and immunohistochemistry analysis.</p><p><strong>Results: </strong>Immunohistochemistry confirmed that in this experiment, a mild LS with retinal immune response and minimal photoreceptor loss occurred. Compared to controls, LS induced an increased concentration in phosphatidylcholines. The concentration in some amino acids and biogenic amines, particularly those related to the nitric oxide pathway (like asymmetric dimethylarginine (ADMA), arginine and citrulline) also increased 1 day after LS. 7 days after LS, the concentration in two sphingomyelins and phenylethylamine was found to be higher. We further found that in controls, retina metabolome was different between males and females: male retinas had an increased concentration in tyrosine, acetyl-ornithine, phosphatidylcholines and (acyl)-carnitines.</p><p><strong>Conclusions: </strong>Besides retinal sexual metabolic dimorphism, this study shows that preconditioning is mostly associated with re-organisation of lipid metabolism and changes in amino acid composition, likely reflecting the involvement of arginine-dependent NO signalling.</p>","PeriodicalId":144887,"journal":{"name":"Metabolomics : Official journal of the Metabolomic Society","volume":" ","pages":"22"},"PeriodicalIF":3.6,"publicationDate":"2017-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s11306-016-1156-9","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35166982","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multilevel pharmacokinetics-driven modeling of metabolomics data.","authors":"Emilia Daghir-Wojtkowiak,&nbsp;Paweł Wiczling,&nbsp;Małgorzata Waszczuk-Jankowska,&nbsp;Roman Kaliszan,&nbsp;Michał Jan Markuszewski","doi":"10.1007/s11306-017-1164-4","DOIUrl":"https://doi.org/10.1007/s11306-017-1164-4","url":null,"abstract":"<p><strong>Introduction: </strong>Multilevel modeling is a quantitative statistical method to investigate variability and relationships between variables of interest, taking into account population structure and dependencies. It can be used for prediction, data reduction and causal inference from experiments and observational studies allowing for more efficient elucidation of knowledge.</p><p><strong>Objectives: </strong>In this study we introduced the concept of multilevel pharmacokinetics (PK)-driven modelling for large-sample, unbalanced and unadjusted metabolomics data comprising nucleoside and creatinine concentration measurements in urine of healthy and cancer patients.</p><p><strong>Methods: </strong>A Bayesian multilevel model was proposed to describe the nucleoside and creatinine concentration ratio considering age, sex and health status as covariates. The predictive performance of the proposed model was summarized via area under the ROC, sensitivity and specificity using external validation.</p><p><strong>Results: </strong>Cancer was associated with an increase in methylthioadenosine/creatinine excretion rate by a factor of 1.42 (1.09-2.03) which constituted the highest increase among all nucleosides. Age influenced nucleosides/creatinine excretion rates for all nucleosides in the same direction which was likely caused by a decrease in creatinine clearance with age. There was a small evidence of sex-related differences for methylthioadenosine. The individual <i>a posteriori</i> prediction of patient classification as area under the ROC with 5th and 95th percentile was 0.57(0.5-0.67) with sensitivity and specificity of 0.59(0.42-0.76) and 0.57(0.45-0.7), respectively suggesting limited usefulness of 13 nucleosides/creatinine urine concentration measurements in predicting disease in this population.</p><p><strong>Conclusion: </strong>Bayesian multilevel pharmacokinetics-driven modeling in metabolomics may be useful in understanding the data and may constitute a new tool for searching towards potential candidates of disease indicators.</p>","PeriodicalId":144887,"journal":{"name":"Metabolomics : Official journal of the Metabolomic Society","volume":" ","pages":"31"},"PeriodicalIF":3.6,"publicationDate":"2017-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s11306-017-1164-4","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34778448","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A metabolomic, geographic, and seasonal analysis of the contribution of pollen-derived adenosine to allergic sensitization.","authors":"Geoffrey A Mueller, Peter M Thompson, Eugene F DeRose, Thomas M O'Connell, Robert E London","doi":"10.1007/s11306-016-1130-6","DOIUrl":"10.1007/s11306-016-1130-6","url":null,"abstract":"<p><strong>Background: </strong>Studies on ragweed and birch pollen extracts suggested that the adenosine content is an important factor in allergic sensitization. However, exposure levels from other pollens and considerations of geographic and seasonal factors have not been evaluated.</p><p><strong>Objective: </strong>This study compared the metabolite profile of pollen species important for allergic disease, specifically measured the adenosine content, and evaluated exposure to pollen-derived adenosine.</p><p><strong>Methods: </strong>An NMR metabolomics approach was used to measure metabolite concentrations in twenty-six pollen extracts. Pollen count data was analyzed from five cities to model exposure.</p><p><strong>Results: </strong>A principal component analysis of the various metabolites identified by NMR showed that pollen extracts could be differentiated primarily by sugar content: glucose, fructose, sucrose, and myo-inositol. In extracts of 10 mg of pollen/ml, the adenosine was highest for grasses (45 μM) followed by trees (23 μM) and weeds (19 μM). Pollen count data showed that tree pollen was typically 5-10 times the amount of other pollens. At the daily peaks of tree, grass, and weed season the pollen-derived adenosine exposure per day is likely to only be 1.1, 0.11, and 0.12 μg, respectively. Seasonal models of pollen exposure and respiration suggest that it would be a rare event limited to tree pollen season for concentrations of pollen-derived adenosine to approach physiological levels.</p><p><strong>Conclusions: </strong>Sugar content and other metabolites may be useful in classifying pollens. Unless other factors create localized exposures that are very different from these models, pollen-derived adenosine is unlikely to be a major factor in allergic sensitization.</p>","PeriodicalId":144887,"journal":{"name":"Metabolomics : Official journal of the Metabolomic Society","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2016-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5546310/pdf/nihms882221.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35403672","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comprehensive Optimization of LC-MS Metabolomics Methods Using Design of Experiments (COLMeD).","authors":"Seth D Rhoades,&nbsp;Aalim M Weljie","doi":"10.1007/s11306-016-1132-4","DOIUrl":"https://doi.org/10.1007/s11306-016-1132-4","url":null,"abstract":"<p><strong>Introduction: </strong>Both reverse-phase and HILIC chemistries are deployed for liquid-chromatography mass spectrometry (LC-MS) metabolomics analyses, however HILIC methods lag behind reverse-phase methods in reproducibility and versatility. Comprehensive metabolomics analysis is additionally complicated by the physiochemical diversity of metabolites and array of tunable analytical parameters.</p><p><strong>Objective: </strong>Our aim was to rationally and efficiently design complementary HILIC-based polar metabolomics methods on multiple instruments using Design of Experiments (DoE).</p><p><strong>Methods: </strong>We iteratively tuned LC and MS conditions on ion-switching triple quadrupole (QqQ) and quadrupole-time-of-flight (qTOF) mass spectrometers through multiple rounds of a workflow we term COLMeD (Comprehensive optimization of LC-MS metabolomics methods using design of experiments). Multivariate statistical analysis guided our decision process in the method optimizations.</p><p><strong>Results: </strong>LC-MS/MS tuning for the QqQ method on serum metabolites yielded a median response increase of 161.5% (p<0.0001) over initial conditions with a 13.3% increase in metabolite coverage. The COLMeD output was benchmarked against two widely used polar metabolomics methods, demonstrating total ion current increases of 105.8% and 57.3%, with median metabolite response increases of 106.1% and 10.3% (p<0.0001 and p<0.05 respectively). For our optimized qTOF method, 22 solvent systems were compared on a standard mix of physiochemically diverse metabolites, followed by COLMeD optimization, yielding a median 29.8% response increase (p<0.0001) over initial conditions.</p><p><strong>Conclusions: </strong>The COLMeD process elucidated response tradeoffs, facilitating improved chromatography and MS response without compromising separation of isobars. COLMeD is efficient, requiring no more than 20 injections in a given DoE round, and flexible, capable of class-specific optimization as demonstrated through acylcarnitine optimization within the QqQ method.</p>","PeriodicalId":144887,"journal":{"name":"Metabolomics : Official journal of the Metabolomic Society","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2016-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s11306-016-1132-4","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34860347","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"1-stearoylglycerol is associated with risk of prostate cancer: results from serum metabolomic profiling.","authors":"A. Mondul, S. Moore, S. Weinstein, S. Männistö, J. Sampson, D. Albanes","doi":"10.1158/1538-7445.AM2014-5068","DOIUrl":"https://doi.org/10.1158/1538-7445.AM2014-5068","url":null,"abstract":"Although prostate cancer is the most commonly diagnosed cancer among men in developed populations, recent recommendations against routine prostate-specific antigen screening have cast doubt on its utility for early detection. We compared the metabolomic profiles of prospectively collected fasting serum from 74 prostate cancer cases and 74 controls selected from the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study cohort of male smokers. Circulating 1-stearoylglycerol (1-SG, or 1-monostearin) was statistically significantly inversely associated with risk of prostate cancer after Bonferroni correction for multiple comparisons (i.e., 420 identified metabolites) (OR=0.34, 95% CI=0.20 - 0.58, p=6.3 × 10-5). The magnitude of this association did not differ by disease aggressiveness and was observed for cases diagnosed up to 23 years after blood collection. Similar but somewhat weaker prostate cancer risk signals were also evident for glycerol and alpha-ketoglutarate. In this population, men with higher serum 1-SG were less likely to develop prostate cancer, supporting a role for dysregulation of lipid metabolism in this malignancy. Additional studies are needed to retest the association and to examine 1-SG for its potential as a prostate cancer early detection marker.","PeriodicalId":144887,"journal":{"name":"Metabolomics : Official journal of the Metabolomic Society","volume":"78 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2014-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"121472961","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lipidomic analysis of variation in response to simvastatin in the Cholesterol and Pharmacogenetics Study.","authors":"Rima Kaddurah-Daouk,&nbsp;Rebecca A Baillie,&nbsp;Hongjie Zhu,&nbsp;Zhao-Bang Zeng,&nbsp;Michelle M Wiest,&nbsp;Uyen Thao Nguyen,&nbsp;Steven M Watkins,&nbsp;Ronald M Krauss","doi":"10.1007/s11306-010-0207-x","DOIUrl":"https://doi.org/10.1007/s11306-010-0207-x","url":null,"abstract":"<p><p>Statins are commonly used for reducing cardiovascular disease risk but therapeutic benefit and reductions in levels of low-density lipoprotein cholesterol (LDL-C) vary among individuals. Other effects, including reductions in C-reactive protein (CRP), also contribute to treatment response. Metabolomics provides powerful tools to map pathways implicated in variation in response to statin treatment. This could lead to mechanistic hypotheses that provide insight into the underlying basis for individual variation in drug response. Using a targeted lipidomics platform, we defined lipid changes in blood samples from the upper and lower tails of the LDL-C response distribution in the Cholesterol and Pharmacogenetics study. Metabolic changes in responders are more comprehensive than those seen in non-responders. Baseline cholesterol ester and phospholipid metabolites correlated with LDL-C response to treatment. CRP response to therapy correlated with baseline plasmalogens, lipids involved in inflammation. There was no overlap of lipids whose changes correlated with LDL-C or CRP responses to simvastatin suggesting that distinct metabolic pathways govern statin effects on these two biomarkers. Metabolic signatures could provide insights about variability in response and mechanisms of action of statins. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s11306-010-0207-x) contains supplementary material, which is available to authorized users.</p>","PeriodicalId":144887,"journal":{"name":"Metabolomics : Official journal of the Metabolomic Society","volume":" ","pages":"191-201"},"PeriodicalIF":3.6,"publicationDate":"2010-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s11306-010-0207-x","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"28969216","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An inter-laboratory comparison demonstrates that [H]-NMR metabolite fingerprinting is a robust technique for collaborative plant metabolomic data collection.","authors":"Jane L Ward, John M Baker, Sonia J Miller, Catherine Deborde, Mickael Maucourt, Benoit Biais, Dominique Rolin, Annick Moing, Sofia Moco, Jacques Vervoort, Arjen Lommen, Hartmut Schäfer, Eberhard Humpfer, Michael H Beale","doi":"10.1007/s11306-010-0200-4","DOIUrl":"10.1007/s11306-010-0200-4","url":null,"abstract":"<p><p>In any metabolomics experiment, robustness and reproducibility of data collection is of vital importance. These become more important in collaborative studies where data is to be collected on multiple instruments. With minimisation of variance in sample preparation and instrument performance it is possible to elucidate even subtle differences in metabolite fingerprints due to genotype or biological treatment. In this paper we report on an inter laboratory comparison of plant derived samples by [(1)H]-NMR spectroscopy across five different sites and within those sites utilising instruments with different probes and magnetic field strengths of 9.4 T (400 MHz), 11.7 T (500 MHz) and 14.1 T (600 MHz). Whilst the focus of the study is on consistent data collection across laboratories, aspects of sample stability and the requirement for sample rotation within the NMR magnet are also discussed. Comparability of the datasets from participating laboratories was exceptionally good and the data were amenable to comparative analysis by multivariate statistics. Field strength differences can be adjusted for in the data pre-processing and multivariate analysis demonstrating that [(1)H]-NMR fingerprinting is the ideal technique for large scale plant metabolomics data collection requiring the participation of multiple laboratories.</p>","PeriodicalId":144887,"journal":{"name":"Metabolomics : Official journal of the Metabolomic Society","volume":" ","pages":"263-273"},"PeriodicalIF":0.0,"publicationDate":"2010-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/30/b8/11306_2010_Article_200.PMC2874487.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"29034646","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Metabolomics of urine for the assessment of microvesicular lipid accumulation in the liver following isoniazid exposure.","authors":"Susan J Sumner, Jason P Burgess, Rodney W Snyder, James A Popp, Timothy R Fennell","doi":"10.1007/s11306-010-0197-8","DOIUrl":"10.1007/s11306-010-0197-8","url":null,"abstract":"<p><p>This study was conducted to develop a noninvasive marker of hepatic microvesicular lipid accumulation (MVLA), a histopathological effect currently diagnosed in humans following liver biopsy. MVLA is detected in animal studies of chemicals and drugs and occurs in some humans exposed to chemicals or pharmaceuticals. Because MVLA is a reversible histopathology, early detection of MVLA using a noninvasive method, could aid clinicians in the treatment of patients taking drugs that are known to induce this injury. Isoniazid (INH) was selected as a model compound for this investigation, because MVLA occurs in tuberculosis (TB) patients treated with a combination therapy, which includes INH. This study used male rats dosed daily with INH at 0, 10, or 300 mg/kg/day for up to 8 days. Urine, blood, and liver were obtained following 1 and 8 days. NMR metabolomics of urine revealed markers that correlated (100%) with the findings of MVLA in the right, left, and median liver lobes in 4/9 rats administered the high dose of INH for 8 days. Metabolomics of liver extracts also revealed markers that correlated with the MVLA injury. Serum enzymes that are clinically used to assess liver injury were not consistently correlated to the findings of MVLA. Metabolite changes consistent with the presence of MVLA correlated with interruptions in inositol, carbohydrate, glycerolipid, and glyoxylate metabolism. This study reveals markers that could find pre-clinical use, provides insights into mechanisms involved in MVLA, and demonstrates the need for the validation of noninvasive MVLA markers in human patients.</p>","PeriodicalId":144887,"journal":{"name":"Metabolomics : Official journal of the Metabolomic Society","volume":" ","pages":"238-249"},"PeriodicalIF":0.0,"publicationDate":"2010-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2968713/pdf/nihms190332.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"29452576","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Histone deacetylase inhibition results in a common metabolic profile associated with HT29 differentiation.","authors":"Gema Alcarraz-Vizán,&nbsp;Joan Boren,&nbsp;Wai-Nang Paul Lee,&nbsp;Marta Cascante","doi":"10.1007/s11306-009-0192-0","DOIUrl":"https://doi.org/10.1007/s11306-009-0192-0","url":null,"abstract":"<p><p>Cell differentiation is an orderly process that begins with modifications in gene expression. This process is regulated by the acetylation state of histones. Removal of the acetyl groups of histones by specific enzymes (histone deacetylases, HDAC) usually downregulates expression of genes that can cause cells to differentiate, and pharmacological inhibitors of these enzymes have been shown to induce differentiation in several colon cancer cell lines. Butyrate at high (mM) concentration is both a precursor for acetyl-CoA and a known HDAC inhibitor that induces cell differentiation in colon cells. The dual role of butyrate raises the question whether its effects on HT29 cell differentiation are due to butyrate metabolism or to its HDAC inhibitor activity. To distinguish between these two possibilities, we used a tracer-based metabolomics approach to compare the metabolic changes induced by two different types of HDAC inhibitors (butyrate and the non-metabolic agent trichostatin A) and those induced by other acetyl-CoA precursors that do not inhibit HDAC (caprylic and capric acids). [1,2-(13)C(2)]-d-glucose was used as a tracer and its redistribution among metabolic intermediates was measured to estimate the contribution of glycolysis, the pentose phosphate pathway and the Krebs cycle to the metabolic profile of HT29 cells under the different treatments. The results demonstrate that both HDAC inhibitors (trichostatin A and butyrate) induce a common metabolic profile that is associated with histone deacetylase inhibition and differentiation of HT29 cells whereas the metabolic effects of acetyl-CoA precursors are different from those of butyrate. The experimental findings support the concept of crosstalk between metabolic and cell signalling events, and provide an experimental approach for the rational design of new combined therapies that exploit the potential synergism between metabolic adaptation and cell differentiation processes through modification of HDAC activity.</p>","PeriodicalId":144887,"journal":{"name":"Metabolomics : Official journal of the Metabolomic Society","volume":" ","pages":"229-237"},"PeriodicalIF":3.6,"publicationDate":"2010-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s11306-009-0192-0","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"28968181","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Decision tree supported substructure prediction of metabolites from GC-MS profiles.","authors":"Jan Hummel,&nbsp;Nadine Strehmel,&nbsp;Joachim Selbig,&nbsp;Dirk Walther,&nbsp;Joachim Kopka","doi":"10.1007/s11306-010-0198-7","DOIUrl":"https://doi.org/10.1007/s11306-010-0198-7","url":null,"abstract":"<p><p>Gas chromatography coupled to mass spectrometry (GC-MS) is one of the most widespread routine technologies applied to the large scale screening and discovery of novel metabolic biomarkers. However, currently the majority of mass spectral tags (MSTs) remains unidentified due to the lack of authenticated pure reference substances required for compound identification by GC-MS. Here, we accessed the information on reference compounds stored in the Golm Metabolome Database (GMD) to apply supervised machine learning approaches to the classification and identification of unidentified MSTs without relying on library searches. Non-annotated MSTs with mass spectral and retention index (RI) information together with data of already identified metabolites and reference substances have been archived in the GMD. Structural feature extraction was applied to sub-divide the metabolite space contained in the GMD and to define the prediction target classes. Decision tree (DT)-based prediction of the most frequent substructures based on mass spectral features and RI information is demonstrated to result in highly sensitive and specific detections of sub-structures contained in the compounds. The underlying set of DTs can be inspected by the user and are made available for batch processing via SOAP (Simple Object Access Protocol)-based web services. The GMD mass spectral library with the integrated DTs is freely accessible for non-commercial use at http://gmd.mpimp-golm.mpg.de/. All matching and structure search functionalities are available as SOAP-based web services. A XML + HTTP interface, which follows Representational State Transfer (REST) principles, facilitates read-only access to data base entities.</p>","PeriodicalId":144887,"journal":{"name":"Metabolomics : Official journal of the Metabolomic Society","volume":" ","pages":"322-333"},"PeriodicalIF":3.6,"publicationDate":"2010-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s11306-010-0198-7","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"29034644","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}