Integrative Molecular Phenotyping
INTEGRATIVE MOLECULAR
PHENOTYPING
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY

PubMed

PubMed
NCBI: db=pubmed; Term=metabolomics
Updated: 9 min 47 sec ago

Minimal Information About an Immuno-Peptidomics Experiment (MIAIPE).

Thu, 24/05/2018 - 13:50
Related Articles Minimal Information About an Immuno-Peptidomics Experiment (MIAIPE). Proteomics. 2018 May 23;:e1800110 Authors: Lill JR, van Veelen PA, Tenzer S, Admon A, Caron E, Elias J, Heck AJR, Marcilla M, Marino F, Müller M, Peters B, Purcell A, Sette A, Sturm T, Ternette N, Vizcaíno JA, Bassani-Sternberg M Abstract Minimal Information about an Immuno-Peptidomics Experiment (MIAIPE) is an initiative of the members of the Human Immuno-Peptidome Project (HIPP), an international program organized by the Human Proteome Organization (HUPO). The aim of the MIAIPE guidelines is to deliver technical guidelines representing the minimal information required to sufficiently support the evaluation and interpretation of immunopeptidomics experiments. The MIAIPE document has been designed to report essential information about sample preparation, mass spectrometric measurement and associated mass spectrometry (MS)-related bioinformatics aspects that are unique to immunopeptidomics and may not be covered by the general proteomics MIAPE (Minimal Information About a Proteomics Experiment) guidelines. This article is protected by copyright. All rights reserved. PMID: 29791771 [PubMed - as supplied by publisher]

SHMT2 and the BRCC36/BRISC deubiquitinase regulate HIV-1 Tat K63-ubiquitylation and destruction by autophagy.

Thu, 24/05/2018 - 13:50
Related Articles SHMT2 and the BRCC36/BRISC deubiquitinase regulate HIV-1 Tat K63-ubiquitylation and destruction by autophagy. PLoS Pathog. 2018 May 23;14(5):e1007071 Authors: Xu M, Moresco JJ, Chang M, Mukim A, Smith D, Diedrich JK, Yates JR, Jones KA Abstract HIV-1 Tat is a key regulator of viral transcription, however little is known about the mechanisms that control its turnover in T cells. Here we use a novel proteomics technique, called DiffPOP, to identify the molecular target of JIB-04, a small molecule compound that potently and selectively blocks HIV-1 Tat expression, transactivation, and virus replication in T cell lines. Mass-spectrometry analysis of whole-cell extracts from 2D10 Jurkat T cells revealed that JIB-04 targets Serine Hydroxymethyltransferase 2 (SHMT2), a regulator of glycine biosynthesis and an adaptor for the BRCC36 K63Ub-specific deubiquitinase in the BRISC complex. Importantly, knockdown of SHMT1,2 or BRCC36, or exposure of cells to JIB-04, strongly increased Tat K63Ub-dependent destruction via autophagy. Moreover, point mutation of multiple lysines in Tat, or knockdown of BRCC36 or SHMT1,2, was sufficient to prevent destruction of Tat by JIB-04. We conclude that HIV-1 Tat levels are regulated through K63Ub-selective autophagy mediated through SHMT1,2 and the BRCC36 deubiquitinase. PMID: 29791506 [PubMed - as supplied by publisher]

The Galaxy platform for accessible, reproducible and collaborative biomedical analyses: 2018 update.

Thu, 24/05/2018 - 13:50
Related Articles The Galaxy platform for accessible, reproducible and collaborative biomedical analyses: 2018 update. Nucleic Acids Res. 2018 May 22;: Authors: Afgan E, Baker D, Batut B, van den Beek M, Bouvier D, Cech M, Chilton J, Clements D, Coraor N, Grüning BA, Guerler A, Hillman-Jackson J, Hiltemann S, Jalili V, Rasche H, Soranzo N, Goecks J, Taylor J, Nekrutenko A, Blankenberg D Abstract Galaxy (homepage: https://galaxyproject.org, main public server: https://usegalaxy.org) is a web-based scientific analysis platform used by tens of thousands of scientists across the world to analyze large biomedical datasets such as those found in genomics, proteomics, metabolomics and imaging. Started in 2005, Galaxy continues to focus on three key challenges of data-driven biomedical science: making analyses accessible to all researchers, ensuring analyses are completely reproducible, and making it simple to communicate analyses so that they can be reused and extended. During the last two years, the Galaxy team and the open-source community around Galaxy have made substantial improvements to Galaxy's core framework, user interface, tools, and training materials. Framework and user interface improvements now enable Galaxy to be used for analyzing tens of thousands of datasets, and >5500 tools are now available from the Galaxy ToolShed. The Galaxy community has led an effort to create numerous high-quality tutorials focused on common types of genomic analyses. The Galaxy developer and user communities continue to grow and be integral to Galaxy's development. The number of Galaxy public servers, developers contributing to the Galaxy framework and its tools, and users of the main Galaxy server have all increased substantially. PMID: 29790989 [PubMed - as supplied by publisher]

Target-decoy Based False Discovery Rate Estimation for Large-scale Metabolite Identification.

Thu, 24/05/2018 - 13:50
Related Articles Target-decoy Based False Discovery Rate Estimation for Large-scale Metabolite Identification. J Proteome Res. 2018 May 23;: Authors: Wang X, Jones DR, Shaw TI, Cho JH, Wang Y, Tan H, Xie B, Zhou S, Li Y, Peng J Abstract Metabolite identification is a crucial step in mass spectrometry (MS)-based metabolomics. However, it is still challenging to assess the confidence of assigned metabolites. In this study, we report a novel method for estimating false discovery rate (FDR) of metabolite assignment with a target-decoy strategy, in which the decoys are generated through violating the octet rule of chemistry by adding small odd numbers of hydrogen atoms. The target-decoy strategy was integrated into JUMPm, an automated metabolite identification pipeline for large-scale MS analysis, and was also evaluated with two other metabolomics tools, mzMatch and mzMine 2. The reliability of FDR calculation was examined by false datasets, which were simulated by altering MS1 or MS2 spectra. Finally, we used the JUMPm pipeline coupled with the target-decoy strategy to process unlabeled and stable-isotope labeled metabolomic datasets. The results demonstrate that the target-decoy strategy is a simple and effective method for evaluating the confidence of high-throughput metabolite identification. PMID: 29790753 [PubMed - as supplied by publisher]

Metabolomics reveals the key role of oxygen metabolism in the heat susceptibility of an alpine dwelling ghost moth, Thitarodes xiaojinensis (Lepidoptera: Hepialidae).

Thu, 24/05/2018 - 13:50
Related Articles Metabolomics reveals the key role of oxygen metabolism in the heat susceptibility of an alpine dwelling ghost moth, Thitarodes xiaojinensis (Lepidoptera: Hepialidae). Insect Sci. 2018 May 23;: Authors: Zhu W, Meng Q, Zhang H, Wang ML, Li X, Wang HT, Zhou GL, Miao L, Qin QL, Zhang JH Abstract Ghost moths inhabiting the alpine meadows of the Tibetan Plateau are cold-adapted stenothermal organisms that are susceptible to heat (dead within 7 days of 27 °C exposure). Exploring the metabolic basis of their heat susceptibility would extend our understanding of the thermal biology of alpine dwelling invertebrates. Here, gas chromatography-mass spectrometry-based metabolomics was combined with physiological and transcriptional approaches to determine the metabolic mechanisms of heat susceptibility in Thitarodes xiaojinensis larvae. The metabolomics results showed that 27 °C heat stress impaired the Krebs cycle and lipolysis in T. xiaojinensis larvae, as demonstrated by the accumulation of intermediary metabolites. In addition, carbohydrate reserves were highly and exclusively consumed, and an anaerobic product, lactate, accumulated. This evidence suggested a strong reliance on glycolysis to generate energy anaerobically. The respiration rate and enzymatic activity test results indicated a deficiency in O2 metabolism; in addition, the Krebs cycle capacity was not lowered, and the metabolic flux through aerobic pathways was limited. These findings were further supported by the occurrence of hypoxia symptoms in midgut mitochondria (vacuolation and swelling) and increased transcription of hypoxia-induced factor 1-α. Overall, heat stress caused O2 limitation and depressed the overall intensity of aerobic metabolism in ghost moths, and less efficient anaerobic glycolysis was activated to sustain their energy supply. After the carbohydrates became limited, the energy supply became deficient. Our study presented a comprehensive metabolic explanation for the heat susceptibility of ghost moths and revealed the relationship between O2 metabolism and heat susceptibility in these larvae. This article is protected by copyright. All rights reserved. PMID: 29790270 [PubMed - as supplied by publisher]

Metabolic remodeling of substrate utilization during heart failure progression.

Thu, 24/05/2018 - 13:50
Related Articles Metabolic remodeling of substrate utilization during heart failure progression. Heart Fail Rev. 2018 May 23;: Authors: Chen L, Song J, Hu S Abstract Heart failure (HF) is a clinical syndrome caused by a decline in cardiac systolic or diastolic function, which leaves the heart unable to pump enough blood to meet the normal physiological requirements of the human body. It is a serious disease burden worldwide affecting nearly 23 million patients. The concept that heart failure is "an engine out of fuel" has been generally accepted and metabolic remodeling has been recognized as an important aspect of this condition; it is characterized by defects in energy production and changes in metabolic pathways involved in the regulation of essential cellular functions such as the process of substrate utilization, the tricarboxylic acid cycle, oxidative phosphorylation, and high-energy phosphate metabolism. Advances in second-generation sequencing, proteomics, and metabolomics have made it possible to perform comprehensive tests on genes and metabolites that are crucial in the process of HF, thereby providing a clearer and comprehensive understanding of metabolic remodeling during HF. In recent years, new metabolic changes such as ketone bodies and branched-chain amino acids were demonstrated as alternative substrates in end-stage HF. This systematic review focuses on changes in metabolic substrate utilization during the progression of HF and the underlying regulatory mechanisms. Accordingly, the conventional concepts of metabolic remodeling characteristics are reviewed, and the latest developments, particularly multi-omics studies, are compiled. PMID: 29789980 [PubMed - as supplied by publisher]

Association of Plasma Lipids and Polar Metabolites with Low Bone Mineral Density in Singaporean-Chinese Menopausal Women: A Pilot Study.

Thu, 24/05/2018 - 13:50
Related Articles Association of Plasma Lipids and Polar Metabolites with Low Bone Mineral Density in Singaporean-Chinese Menopausal Women: A Pilot Study. Int J Environ Res Public Health. 2018 May 22;15(5): Authors: Cabrera D, Kruger M, Wolber FM, Roy NC, Totman JJ, Henry CJ, Cameron-Smith D, Fraser K Abstract The diagnosis of osteoporosis is mainly based on clinical examination and bone mineral density assessments. The present pilot study compares the plasma lipid and polar metabolite profiles in blood plasma of 95 Singaporean-Chinese (SC) menopausal women with normal and low bone mineral density (BMD) using an untargeted metabolomic approach. The primary finding of this study was the association between lipids and femoral neck BMD in SC menopausal women. Twelve lipids were identified to be associated with low BMD by the orthogonal partial least squares (OPLS) model. Plasma concentrations of eight glycerophospholipid, glycerolipid, and sphingolipid species were significantly lower in menopausal women with low BMD but higher in two glycerophospholipid species (phosphatidylinositol and phosphatidic acid). Further, this study found no significant differences in plasma amino acid metabolites. However, trends for lower 4-aminobutyric acid, turanose, proline, aminopropionitrile, threonine, and methionine were found in women with low BMD. This pilot study identified associations between lipid metabolism and femoral neck BMD in SC women. Further studies are required on larger populations for evaluating the bone health effect of these compounds and their usefulness as clinical biomarkers for osteoporosis prediction in women. PMID: 29789485 [PubMed - in process]

Concepts and Methods to Access Novel Antibiotics from Actinomycetes.

Thu, 24/05/2018 - 13:50
Related Articles Concepts and Methods to Access Novel Antibiotics from Actinomycetes. Antibiotics (Basel). 2018 May 22;7(2): Authors: Hug JJ, Bader CD, Remškar M, Cirnski K, Müller R Abstract Actinomycetes have been proven to be an excellent source of secondary metabolites for more than half a century. Exhibiting various bioactivities, they provide valuable approved drugs in clinical use. Most microorganisms are still untapped in terms of their capacity to produce secondary metabolites, since only a small fraction can be cultured in the laboratory. Thus, improving cultivation techniques to extend the range of secondary metabolite producers accessible under laboratory conditions is an important first step in prospecting underexplored sources for the isolation of novel antibiotics. Currently uncultured actinobacteria can be made available by bioprospecting extreme or simply habitats other than soil. Furthermore, bioinformatic analysis of genomes reveals most producers to harbour many more biosynthetic gene clusters than compounds identified from any single strain, which translates into a silent biosynthetic potential of the microbial world for the production of yet unknown natural products. This review covers discovery strategies and innovative methods recently employed to access the untapped reservoir of natural products. The focus is the order of actinomycetes although most approaches are similarly applicable to other microbes. Advanced cultivation methods, genomics- and metagenomics-based approaches, as well as modern metabolomics-inspired methods are highlighted to emphasise the interplay of different disciplines to improve access to novel natural products. PMID: 29789481 [PubMed]

Circulating Metabolites Associated with Alcohol Intake in the European Prospective Investigation into Cancer and Nutrition Cohort.

Thu, 24/05/2018 - 13:50
Related Articles Circulating Metabolites Associated with Alcohol Intake in the European Prospective Investigation into Cancer and Nutrition Cohort. Nutrients. 2018 May 22;10(5): Authors: van Roekel EH, Trijsburg L, Assi N, Carayol M, Achaintre D, Murphy N, Rinaldi S, Schmidt JA, Stepien M, Kaaks R, Kühn T, Boeing H, Iqbal K, Palli D, Krogh V, Tumino R, Ricceri F, Panico S, Peeters PH, Bueno-de-Mesquita B, Ardanaz E, Lujan-Barroso L, Quirós JR, Huerta JM, Molina-Portillo E, Dorronsoro M, Tsilidis KK, Riboli E, Rostgaard-Hansen AL, Tjønneland A, Overvad K, Weiderpass E, Boutron-Ruault MC, Severi G, Trichopoulou A, Karakatsani A, Kotanidou A, Håkansson A, Malm J, Weijenberg MP, Gunter MJ, Jenab M, Johansson M, Travis RC, Scalbert A, Ferrari P Abstract Identifying the metabolites associated with alcohol consumption may provide insights into the metabolic pathways through which alcohol may affect human health. We studied associations of alcohol consumption with circulating concentrations of 123 metabolites among 2974 healthy participants from the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Alcohol consumption at recruitment was self-reported through dietary questionnaires. Metabolite concentrations were measured by tandem mass spectrometry (BIOCRATES AbsoluteIDQTM p180 kit). Data were randomly divided into discovery (2/3) and replication (1/3) sets. Multivariable linear regression models were used to evaluate confounder-adjusted associations of alcohol consumption with metabolite concentrations. Metabolites significantly related to alcohol intake in the discovery set (FDR q-value < 0.05) were further tested in the replication set (Bonferroni-corrected p-value < 0.05). Of the 72 metabolites significantly related to alcohol intake in the discovery set, 34 were also significant in the replication analysis, including three acylcarnitines, the amino acid citrulline, four lysophosphatidylcholines, 13 diacylphosphatidylcholines, seven acyl-alkylphosphatidylcholines, and six sphingomyelins. Our results confirmed earlier findings that alcohol consumption was associated with several lipid metabolites, and possibly also with specific acylcarnitines and amino acids. This provides further leads for future research studies aiming at elucidating the mechanisms underlying the effects of alcohol in relation to morbid conditions. PMID: 29789452 [PubMed - in process]

Method selectivity evaluation using the co-feature ratio in LC/MS metabolomics: Comparison of HILIC stationary phase performance for the analysis of plasma, urine and cell extracts.

Thu, 24/05/2018 - 13:50
Related Articles Method selectivity evaluation using the co-feature ratio in LC/MS metabolomics: Comparison of HILIC stationary phase performance for the analysis of plasma, urine and cell extracts. J Chromatogr A. 2018 May 04;: Authors: Elmsjö A, Haglöf J, Engskog MKR, Erngren I, Nestor M, Arvidsson T, Pettersson C Abstract Evaluation of the chromatographic separation in metabolomics studies has primarily been done using preselected sets of standards or by counting the number of detected features. An alternative approach is to calculate each feature's co-feature ratio, which is a combined selectivity measurement for the separation (i.e. extent of co-elution) and the MS-signal (i.e. adduct formation and in-source fragmentation). The aim of this study was to demonstrate how the selectivity of different HILIC stationary phases can be evaluated using the co-feature ratio approach. The study was based on three sample types; plasma, urine and cell extracts. Samples were analyzed on an UHPLC-ESI-Q-ToF system using an amide, a bare silica and a sulfobetaine stationary phase. For each feature, a co-feature ratio was calculated and used for multivariate analysis of the selectivity differences between the three stationary phases. Unsupervised PCA models indicated that the co-feature ratios were highly dependent on type of stationary phase. For several metabolites a 15-30 fold difference in the co-feature ratio were observed between the stationary phases. Observed selectivity differences related primarily to the retention patterns of unwanted matrix components such as inorganic salts (detected as salt clusters), glycerophospholipids, and polyethylene glycols. These matrix components affected the signal intensity of co-eluting metabolites by interfering with the ionization efficiency and/or their adduct formation. Furthermore, the retention pattern of these matrix components had huge influence on the number of detected features. The co-feature ratio approach has successfully been applied for evaluation of the selectivity performance of three HILIC stationary phases. The co-feature ratio could therefore be used in metabolomics for developing selective methods fit for their purpose, thereby avoiding generic analytical approaches, which are often biased, as type and amount of interfering matrix components are metabolome dependent. PMID: 29789170 [PubMed - as supplied by publisher]

Effects of low-to-moderate alcohol supplementation on urinary estrogen metabolites in postmenopausal women in a controlled feeding study.

Thu, 24/05/2018 - 13:50
Related Articles Effects of low-to-moderate alcohol supplementation on urinary estrogen metabolites in postmenopausal women in a controlled feeding study. Cancer Med. 2017 Oct;6(10):2419-2423 Authors: Mahabir S, Pfeiffer R, Xu X, Baer DJ, Taylor PR Abstract Heavy alcohol drinking is associated with increased breast cancer risk, but associations with low-to-moderate alcohol consumption are less clear and the biological mechanisms are not well defined. The objective of this study was to evaluate the effects of 8 weeks of low (15 g/d) and moderate (30 g/d) alcohol ingestion on concentrations of 15 urinary estrogen metabolites (EMs) in postmenopausal women (n = 51) in a controlled feeding study with a randomized crossover design. Compared to no alcohol, 15 g/day for 8 weeks had no effect on urinary EMs. However, compared to no alcohol, 30 g/day for 8 weeks decreased urinary 2-hydroestrone (2-OHE1) by 3.3% (P = 0.055) and increased 16-epiestriol (16-EpiE3) by 26.6% (P = 0.037). Trends for reduced urinary 2-OHE1 (P = 0.045), reduced ratio of 2-OH:16OH pathways (P = 0.008), and increased 16-EpiE3 (P = 0.035) were observed as alcohol ingestion increased from 0 g to 15 g to 30 g/d. Moderate alcohol consumption for 8 weeks had modest effects on urinary concentrations of 2-OHE1 and 16-EpiE3 among postmenopausal women in a carefully controlled feeding study. PMID: 28879665 [PubMed - indexed for MEDLINE]

Efficient Mitochondrial Glutamine Targeting Prevails Over Glioblastoma Metabolic Plasticity.

Thu, 24/05/2018 - 13:50
Related Articles Efficient Mitochondrial Glutamine Targeting Prevails Over Glioblastoma Metabolic Plasticity. Clin Cancer Res. 2017 Oct 15;23(20):6292-6304 Authors: Oizel K, Chauvin C, Oliver L, Gratas C, Geraldo F, Jarry U, Scotet E, Rabe M, Alves-Guerra MC, Teusan R, Gautier F, Loussouarn D, Compan V, Martinou JC, Vallette FM, Pecqueur C Abstract Purpose: Glioblastoma (GBM) is the most common and malignant form of primary human brain tumor in adults, with an average survival at diagnosis of 18 months. Metabolism is a new attractive therapeutic target in cancer; however, little is known about metabolic heterogeneity and plasticity within GBM tumors. We therefore aimed to investigate metabolic phenotyping of primary cultures in the context of molecular tumor heterogeneity to provide a proof of concept for personalized metabolic targeting of GBM.Experimental Design: We have analyzed extensively several primary GBM cultures using transcriptomics, metabolic phenotyping assays, and mitochondrial respirometry.Results: We found that metabolic phenotyping clearly identifies 2 clusters, GLNHigh and GLNLow, mainly based on metabolic plasticity and glutamine (GLN) utilization. Inhibition of glutamine metabolism slows the in vitro and in vivo growth of GLNHigh GBM cultures despite metabolic adaptation to nutrient availability, in particular by increasing pyruvate shuttling into mitochondria. Furthermore, phenotypic and molecular analyses show that highly proliferative GLNHigh cultures are CD133neg and display a mesenchymal signature in contrast to CD133pos GLNLow GBM cells.Conclusions: Our results show that metabolic phenotyping identified an essential metabolic pathway in a GBM cell subtype, and provide a proof of concept for theranostic metabolic targeting. Clin Cancer Res; 23(20); 6292-304. ©2017 AACR. PMID: 28720668 [PubMed - indexed for MEDLINE]

Targeted Exome Sequencing of Krebs Cycle Genes Reveals Candidate Cancer-Predisposing Mutations in Pheochromocytomas and Paragangliomas.

Thu, 24/05/2018 - 13:50
Related Articles Targeted Exome Sequencing of Krebs Cycle Genes Reveals Candidate Cancer-Predisposing Mutations in Pheochromocytomas and Paragangliomas. Clin Cancer Res. 2017 Oct 15;23(20):6315-6324 Authors: Remacha L, Comino-Méndez I, Richter S, Contreras L, Currás-Freixes M, Pita G, Letón R, Galarreta A, Torres-Pérez R, Honrado E, Jiménez S, Maestre L, Moran S, Esteller M, Satrústegui J, Eisenhofer G, Robledo M, Cascón A Abstract Purpose: Mutations in Krebs cycle genes are frequently found in patients with pheochromocytomas/paragangliomas. Disruption of SDH, FH or MDH2 enzymatic activities lead to accumulation of specific metabolites, which give rise to epigenetic changes in the genome that cause a characteristic hypermethylated phenotype. Tumors showing this phenotype, but no alterations in the known predisposing genes, could harbor mutations in other Krebs cycle genes.Experimental Design: We used downregulation and methylation of RBP1, as a marker of a hypermethylation phenotype, to select eleven pheochromocytomas and paragangliomas for targeted exome sequencing of a panel of Krebs cycle-related genes. Methylation profiling, metabolite assessment and additional analyses were also performed in selected cases.Results: One of the 11 tumors was found to carry a known cancer-predisposing somatic mutation in IDH1 A variant in GOT2, c.357A>T, found in a patient with multiple tumors, was associated with higher tumor mRNA and protein expression levels, increased GOT2 enzymatic activity in lymphoblastic cells, and altered metabolite ratios both in tumors and in GOT2 knockdown HeLa cells transfected with the variant. Array methylation-based analysis uncovered a somatic epigenetic mutation in SDHC in a patient with multiple pheochromocytomas and a gastrointestinal stromal tumor. Finally, a truncating germline IDH3B mutation was found in a patient with a single paraganglioma showing an altered α-ketoglutarate/isocitrate ratio.Conclusions: This study further attests to the relevance of the Krebs cycle in the development of PCC and PGL, and points to a potential role of other metabolic enzymes involved in metabolite exchange between mitochondria and cytosol. Clin Cancer Res; 23(20); 6315-24. ©2017 AACR. PMID: 28720665 [PubMed - indexed for MEDLINE]

A joint analysis of transcriptomic and metabolomic data uncovers enhanced enzyme-metabolite coupling in breast cancer.

Thu, 24/05/2018 - 13:50
Related Articles A joint analysis of transcriptomic and metabolomic data uncovers enhanced enzyme-metabolite coupling in breast cancer. Sci Rep. 2016 07 13;6:29662 Authors: Auslander N, Yizhak K, Weinstock A, Budhu A, Tang W, Wang XW, Ambs S, Ruppin E Abstract Disrupted regulation of cellular processes is considered one of the hallmarks of cancer. We analyze metabolomic and transcriptomic profiles jointly collected from breast cancer and hepatocellular carcinoma patients to explore the associations between the expression of metabolic enzymes and the levels of the metabolites participating in the reactions they catalyze. Surprisingly, both breast cancer and hepatocellular tumors exhibit an increase in their gene-metabolites associations compared to noncancerous adjacent tissues. Following, we build predictors of metabolite levels from the expression of the enzyme genes catalyzing them. Applying these predictors to a large cohort of breast cancer samples we find that depleted levels of key cancer-related metabolites including glucose, glycine, serine and acetate are significantly associated with improved patient survival. Thus, we show that the levels of a wide range of metabolites in breast cancer can be successfully predicted from the transcriptome, going beyond the limited set of those measured. PMID: 27406679 [PubMed - indexed for MEDLINE]

metabolomics; +34 new citations

Wed, 23/05/2018 - 16:26
34 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results: metabolomics These pubmed results were generated on 2018/05/23PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

metabolomics; +34 new citations

Wed, 23/05/2018 - 13:22
34 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results: metabolomics These pubmed results were generated on 2018/05/23PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

metabolomics; +16 new citations

Tue, 22/05/2018 - 16:10
16 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results: metabolomics These pubmed results were generated on 2018/05/22PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

metabolomics; +16 new citations

Tue, 22/05/2018 - 13:10
16 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results: metabolomics These pubmed results were generated on 2018/05/22PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

Oral ibuprofen differentially affects plasma and sweat lipid mediator profiles in healthy adult males.

Mon, 21/05/2018 - 15:45
Related Articles Oral ibuprofen differentially affects plasma and sweat lipid mediator profiles in healthy adult males. Prostaglandins Other Lipid Mediat. 2018 May 17;: Authors: Agrawal K, Bosviel R, Piccolo BD, Newman JW Abstract Sweat contains a variety of lipid mediators, but whether they originate from the plasma filtrate or from the cutaneous sweat glandular tissues themselves is unknown. To explore this knowledge gap, we collected plasma and sweat from healthy men (n = 9) immediately before and 0.5, 2 and 4 h after oral administration of 400 mg ibuprofen. Of the over 100 lipid mediators assayed by liquid chromatography-tandem mass spectrometry, ~45 were detected in both plasma and sweat, and 36 were common to both matrices. However, baseline concentrations in each matrix were not correlated and metabolite relative abundances between matrices differed. Oral ibuprofen administration altered sweat lipid mediators, reducing prostaglandin E2, linoleoylethanolamide, and oleoylethanolamide, while increasing 11-hydroxyeicosatetraenoic acid, and causing transient changes in 9-nitrooleate, N-arachidonylglycine and 20-hydroxyeicosatetraenoic acid. Meanwhile, plasma N-acylethanolamide concentrations increased with ibuprofen administration. These results suggest that sweat and plasma differentially reflect biochemical changes due to oral ibuprofen administration, and that plasma is unlikely to be the predominant source of the sweat lipid mediator profile. PMID: 29778785 [PubMed - as supplied by publisher]

Plasma metabolic changes in Chinese HIV-infected patients receiving lopinavir/ritonavir based treatment: Implications for HIV precision therapy.

Sun, 20/05/2018 - 12:25
Related Articles Plasma metabolic changes in Chinese HIV-infected patients receiving lopinavir/ritonavir based treatment: Implications for HIV precision therapy. Cytokine. 2018 May 16;110:204-212 Authors: Li X, Wu T, Jiang Y, Zhang Z, Han X, Geng W, Ding H, Kang J, Wang Q, Shang H Abstract OBJECTIVES: The goal of this study is to profile the metabolic changes in the plasma of HIV patients receiving lopinavir/ritonavir (LPV/r)-based highly active antiretroviral therapy (HAART) relative to their treatment-naïve phase, aimed to identify precision therapy for HIV for improving prognosis and predicting dyslipidemia caused by LPV/r. METHODS: 38 longitudinal plasma samples were collected from 19 HIV-infected patients both before and after antiretroviral therapy, and 18 samples from healthy individuals were used as controls. Untargeted metabolomics profiling of these plasma samples was performed using liquid chromatography-mass spectrometry (LC-MS) and gas chromatography-mass spectrometry (GC-MS). RESULTS: A total of 331 compounds of known identity were detected among these metabolites, a 67-metabolite signature mainly mapping to tryptophan, histidine, acyl carnitine, ketone bodies and fatty acid metabolism distinguished HIV patients from healthy controls. The levels of 19 out of the 67 altered metabolites including histidine, kynurenine, and 3-hydroxybutyrate (BHBA), recovered after LPV/r-based antiretroviral therapy, and histidine was positively correlated with the presence of CD4 + T lymphocytes. Furthermore, using receiver operating characteristic (ROC) analyses, we discovered that butyrylcarnitine in combination with myristic acid from plasma in treatment-naïve patients could predict dyslipidemia caused by LPV/r with 87% accuracy. CONCLUSIONS: Metabolites alterations in treatment-naïve HIV patients may indicate an inflammatory, oxidative state and mitochondrial dysfunction that is permissive for disease progression. Histidine may provide a specific protective function for HIV patients. Besides, elevated fatty acids levels including butyrylcarnitine and myristic acid after infection may indicate patients at risk of suffering from dyslipidemia after LPV/r-based HAART. PMID: 29778008 [PubMed - as supplied by publisher]

Pages

1 2 3 4 5 6 7 8 9 next › last »