PubMed

Related Articles [OMICS AND BIG DATA, MAJOR ADVANCES TOWARDS PERSONALIZED MEDICINE OF THE FUTURE?]. Rev Med Liege. 2015 May-Jun;70(5-6):262-8 Authors: Scheen AJ Abstract The increasing interest for personalized medicine evolves together with two major technological advances. First, the new-generation, rapid and less expensive, DNA sequencing method, combined with remarkable progresses in molecular biology leading to the post-genomic era (transcriptomics, proteomics, metabolomics). Second, the refinement of computing tools (IT), which allows the immediate analysis of a huge amount of data (especially, those resulting from the omics approaches) and, thus, creates a new universe for medical research, that of <<big data>> analyzed by computerized modelling. This article for scientific communication and popularization briefly describes the main advances in these two fields of interest. These technological progresses are combined with those occurring in communication, which makes possible the development of artificial intelligence. These major advances will most probably represent the grounds of the future personalized medicine. PMID: 26285450 [PubMed - in process]

Related Articles Lipidomics reveals dysfunctional glycosynapses in schizophrenia and the G72/G30 transgenic mouse. Schizophr Res. 2014 Nov;159(2-3):365-9 Authors: Wood PL, Filiou MD, Otte DM, Zimmer A, Turck CW Abstract BACKGROUND: Abnormal structural/functional connectivity has been proposed to underlie the pathophysiology of schizophrenia. However, the biochemical basis of abnormal connectivity remains undefined. METHODS: We undertook a shotgun lipidomic analysis of over 700 lipids across 26 lipid subclasses in the frontal cortex of schizophrenia subjects and hippocampus of G72/G30 transgenic mice. RESULTS: We demonstrate that glycosphingolipids and choline plasmalogens, structural lipid pools in myelin, are significantly elevated in the frontal cortex obtained from patients suffering from schizophrenia and the hippocampus of G72/G30 transgenic mice. CONCLUSIONS: Our data suggest that structural lipid alterations in oligodendrocyte glycosynapses are responsible for dysconnectivity in schizophrenia and that increased expression of G72 protein may play a role in the development of abnormal glycosynapses. PMID: 25263995 [PubMed - indexed for MEDLINE]

Related Articles Breast milk metabolome characterization in a single-phase extraction, multiplatform analytical approach. Anal Chem. 2014 Aug 19;86(16):8245-52 Authors: Villaseñor A, Garcia-Perez I, Garcia A, Posma JM, Fernández-López M, Nicholas AJ, Modi N, Holmes E, Barbas C Abstract Breast milk (BM) is a biofluid that has a fundamental role in early life nutrition and has direct impact on growth, neurodevelopment, and health. Global metabolic profiling is increasingly being utilized to characterize complex metabolic changes in biological samples. However, in order to achieve broad metabolite coverage, it is necessary to employ more than one analytical platform, typically requiring multiple sample preparation protocols. In an effort to improve analytical efficiency and retain comprehensive coverage of the metabolome, a new extraction methodology was developed that successfully retains metabolites from BM in a single-phase using an optimized methyl-tert-butyl ether solvent system. We conducted this single-phase extraction procedure on a representative pool of BM, and characterized the metabolic composition using LC-QTOF-MS and GC-Q-MS for polar and lipidic metabolites. To ensure that the extraction method was reproducible and fit-for-purpose, the analytical procedure was evaluated on both platforms using 18 metabolites selected to cover a range of chromatographic retention times and biochemical classes. Having validated the method, the metabolic signature of BM composition was mapped as a metabolic reaction network highlighting interconnected biological pathways and showing that the LC-MS and GC-MS platforms targeted largely different domains of the network. Subsequently, the same protocol was applied to ascertain compositional differences between BM at week 1 (n = 10) and 4 weeks (n = 9) post-partum. This single-phase approach is more efficient in terms of time, simplicity, cost, and sample volume than the existing two-phase methods and will be suited to high-throughput metabolic profiling studies of BM. PMID: 25058331 [PubMed - indexed for MEDLINE]

Related Articles Metabolic profiling reveals PAFAH1B3 as a critical driver of breast cancer pathogenicity. Chem Biol. 2014 Jul 17;21(7):831-40 Authors: Mulvihill MM, Benjamin DI, Ji X, Le Scolan E, Louie SM, Shieh A, Green M, Narasimhalu T, Morris PJ, Luo K, Nomura DK Abstract Many studies have identified metabolic pathways that underlie cellular transformation, but the metabolic drivers of cancer progression remain less well understood. The Hippo transducer pathway has been shown to confer malignant traits on breast cancer cells. In this study, we used metabolic mapping platforms to identify biochemical drivers of cellular transformation and malignant progression driven through RAS and the Hippo pathway in breast cancer and identified platelet-activating factor acetylhydrolase 1B3 (PAFAH1B3) as a key metabolic driver of breast cancer pathogenicity that is upregulated in primary human breast tumors and correlated with poor prognosis. Metabolomic profiling suggests that PAFAH1B3 inactivation attenuates cancer pathogenicity through enhancing tumor-suppressing signaling lipids. Our studies provide a map of altered metabolism that underlies breast cancer progression and put forth PAFAH1B3 as a critical metabolic node in breast cancer. PMID: 24954006 [PubMed - indexed for MEDLINE]

23 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 2015/08/19PubMed comprises more than 24 million 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.

Metformin and cancer: Between the bioenergetic disturbances and the antifolate activity. Pharmacol Res. 2015 Aug 12; Authors: Jara JA, López-Muñoz R Abstract For decades, metformin has been the first-line drug for the treatment of type II diabetes mellitus, and it thus is the most widely prescribed antihyperglycemic drug. Retrospective studies associate the use of metformin with a reduction in cancer incidence and cancer-related death. However, despite extensive research about the molecular effects of metformin in cancer cells, its mode of action remains controversial. In this review, we summarize the current molecular evidence in an effort to elucidate metformin's mode of action against cancer cells. Some authors describe that metformin acts directly on mitochondria, inhibiting complex I and restricting the cell's ability to cope with energetic stress. Furthermore, as the drug interrupts the tricarboxylic acid cycle, metformin-induced alteration of mitochondrial function leads to a compensatory increase in lactate and glycolytic ATP. It has also been reported that cell cycle arrest, autophagy, apoptosis and cell death induction is mediated by the activation of AMPK and Redd1 proteins, thus inhibiting the mTOR pathway. Additionally, unbiased metabolomics studies have provided strong evidence to support that metformin alters the methionine and folate cycles, with a concomitant decrease in nucleotide synthesis. Indeed, purines such as thymidine or hypoxanthine restore the proliferation of tumor cells treated with metformin in vitro. Consequently, some authors prefer to refer to metformin as an "antimetabolite drug" rather than a "mitochondrial toxin". Finally, we also review the current controversy concerning the relationship between the experimental conditions of in vitro-reported effects and the plasma concentrations achieved by chronic treatment with metformin. PMID: 26277279 [PubMed - as supplied by publisher]

Related Articles Determining Conserved Metabolic Biomarkers from a Million Database Queries. Bioinformatics. 2015 Aug 13; Authors: Kurczy ME, Ivanisevic J, Johnson CH, Uritboonthai W, Hoang L, Fang M, Hicks M, Aldebot A, Rinehart D, Mellander LJ, Tautenhahn R, Patti GJ, Spilker ME, Benton HP, Siuzdak G Abstract MOTIVATION: Metabolite databases provide a unique window into metabolome research allowing the most commonly searched biomarkers to be catalogued. Omic scale metabolite profiling, or metabolomics, is finding increased utility in biomarker discovery largely driven by improvements in analytical technologies and the concurrent developments in bioinformatics. However, the successful translation of biomarkers into clinical or biologically relevant indicators is limited. RESULTS: With the aim of improving the discovery of translatable metabolite biomarkers, we present search analytics for over one million METLIN metabolite database queries. The most common metabolites found in METLIN were cross-correlated against XCMS Online, the widely used cloud-based data processing and pathway analysis platform. Analysis of the METLIN and XCMS common metabolite data has two primary implications: these metabolites, might indicate a conserved metabolic response to stressors and, this data may be used to gauge the relative uniqueness of potential biomarkers. AVAILABILITY AND IMPLEMENTATION: METLIN can be accessed by logging on to: https://metlin.scripps.edu CONTACT: siuzdak@scripps.edu. PMID: 26275895 [PubMed - as supplied by publisher]

Related Articles An untargeted metabolomics-driven approach based on LC-TOF/MS and LC-MS/MS for the screening of xenobiotics and metabolites of Zhi-Zi-Da-Huang decoction in rat plasma. J Pharm Biomed Anal. 2015 Jul 26;115:315-322 Authors: Wu H, Li X, Yan X, An L, Luo K, Shao M, Jiang Y, Xie R, Feng F Abstract Zhi-Zi-Da-Huang decoction (ZZDHD), a typical traditional Chinese medicine prescription, is widely used in clinical practice for the treatment of alcoholic liver disease. However, due to lack of holistic metabolic research, the active ingredients of ZZDHD have not been fully elucidated. It entails a huge obstacle for the quality evaluation, pharmacokinetic studies and clinical-safe medication administration of ZZDHD. In this work, an untargeted metabolomics-driven approach was proposed to rapidly screen and characterize xenobiotics and related metabolites in vivo conducted by LC-TOF/MS and LC-QqQ/MS. The tR-m/z pairs which were present in the ZZDHD-dosed group and absent in the control group could be clearly displayed by XCMS Online platform combined with supervised orthogonal partial least squares discriminant analysis. Among them, a total of 61 ZZDHD-related xenobiotics and metabolites including 34 prototype components and 27 metabolites were rapidly identified or tentatively characterized in rat plasma. The results indicated that iridoid glycosides and monoterpenoids from Gardenia jasminoides Ellis, flavonoid glycosides from Citrus aurantium L., as well as anthraquinones from Rheum palmatum L. were the main absorbed chemical components of ZZDHD. Hydrolysis, glucuronidation and sulfation were the main metabolic pathways of ZZDHD in vivo. The present study provided a solid basis for further revealing the relationship between the xenobiotic metabolome and pharmacological activity of ZZDHD. In addition, the application of untargeted metabolomics-driven approach offers a fresh insight for rapid screening and identifying xenobiotics and metabolites of ZZDHD and other multiherb prescription. PMID: 26275719 [PubMed - as supplied by publisher]

3-H-[1,2]Dithiole as a New Anti-Trypanosoma cruzi Chemotype: Biological and Mechanism of Action Studies. Molecules. 2015;20(8):14595-14610 Authors: Couto M, Sánchez C, Dávila B, Machín V, Varela J, Álvarez G, Cabrera M, Celano L, Aguirre-López B, Cabrera N, de Gómez-Puyou MT, Gómez-Puyou A, Pérez-Montfort R, Cerecetto H, González M Abstract The current pharmacological Chagas disease treatments, using Nifurtimox or Benznidazole, show limited therapeutic results and are associated with potential side effects, like mutagenicity. Using random screening we have identified new chemotypes that were able to inhibit relevant targets of the Trypanosoma cruzi. We found 3H-[1,2]dithioles with the ability to inhibit Trypanosoma cruzi triosephosphate isomerase (TcTIM). Herein, we studied the structural modifications of this chemotype to analyze the influence of volume, lipophilicity and electronic properties in the anti-T. cruzi activity. Their selectivity to parasites vs. mammalian cells was also examined. To get insights into a possible mechanism of action, the inhibition of the enzymatic activity of TcTIM and cruzipain, using the isolated enzymes, and the inhibition of membrane sterol biosynthesis and excreted metabolites, using the whole parasite, were achieved. We found that this structural framework is interesting for the generation of innovative drugs for the treatment of Chagas disease. PMID: 26274947 [PubMed - as supplied by publisher]

Metabolomics confirms that dissolved organic carbon mitigates copper toxicity. Environ Toxicol Chem. 2015 Aug 14; Authors: Taylor NS, Kirwan JA, Yan ND, Viant MR, Gunn JM, McGeer JC Abstract Reductions in atmospheric emissions from the metal smelters in Sudbury, Canada, produced major improvements in acid and metal contamination of local lakes and indirectly increased dissolved organic carbon (DOC) concentrations; however, metal toxicity has remained a persistent problem for aquatic biota. Integrating high-throughput, non-targeted mass spectrometry metabolomics with conventional toxicological measures elucidated the mediating effects of dissolved organic matter (DOM) on the toxicity of Cu to Daphnia pulex-pulicaria, a hybrid isolated from these soft water lakes. Two generations of daphniids were exposed to Cu (0-20 µg/L) at increasing levels of natural DOM (0-4 mg DOC/L). Added DOM reduced Cu toxicity monotonically with LC50 values increasing from 2.3 µg/L Cu without DOM to 22.7 µg/L Cu at 4 mg DOC/L. Reproductive output similarly benefited, increasing with DOM, yet falling with increases in Cu. Second generation reproduction was more impaired than the first generation. DOM had a greater influence than Cu on the metabolic status of the daphniids. Putative identification of metabolite peaks indicated that DOM elevation increased the metabolic energy status of the first generation animals, but this benefit was reduced in the second generation, while evidence of increased oxidative stress was detected. These results indicate that Sudbury's terrestrial ecosystems should be managed to increase aquatic DOM supply to enable daphniid colonists to both survive and foster stable populations. This article is protected by copyright. All rights reserved. PMID: 26274843 [PubMed - as supplied by publisher]

Metabolomics Reveals Metabolically Healthy and Unhealthy Obese Individuals Differ in their Response to a Caloric Challenge. PLoS One. 2015;10(8):e0134613 Authors: Badoud F, Lam KP, Perreault M, Zulyniak MA, Britz-McKibbin P, Mutch DM Abstract OBJECTIVE: To determine if metabolically healthy obese (MHO) individuals have a different metabolic response to a standardized diet compared to lean healthy (LH) and metabolically unhealthy obese (MUO) individuals. METHODS: Thirty adults (35-70 yrs) were classified as LH, MHO, and MUO according to anthropometric and clinical measurements. Participants consumed a standardized high calorie meal (~1330 kcal). Blood glucose and insulin were measured at fasting, and 15, 30, 60, 90 and 120 min postprandially. Additional blood samples were collected for the targeted analysis of amino acids (AAs) and derivatives, and fatty acids (FAs). RESULTS: The postprandial response (i.e., area under the curve, AUC) for serum glucose and insulin were similar between MHO and LH individuals, and significantly lower than MUO individuals (p < 0.05). Minor differences were found in postprandial responses for AAs between MHO and MUO individuals, while three polyunsaturated FAs (linoleic acid, γ-linolenic acid, arachidonic acid) showed smaller changes in serum after the meal in MHO individuals compared to MUO. Fasting levels for various AAs (notably branched-chain AA) and FAs (e.g., saturated myristic and palmitic acids) were found to correlate with glucose and insulin AUC. CONCLUSION: MHO individuals show preserved insulin sensitivity and a greater ability to adapt to a caloric challenge compared to MUO individuals. PMID: 26274804 [PubMed - as supplied by publisher]

Related Articles Untargeted metabolomics studies employing NMR and LC-MS reveal metabolic coupling between Nanoarcheum equitans and its archaeal host Ignicoccus hospitalis. Metabolomics. 2015 Aug 1;11(4):895-907 Authors: Hamerly T, Tripet BP, Tigges M, Giannone RJ, Wurch L, Hettich RL, Podar M, Copié V, Bothner B Abstract Interspecies interactions are the basis of microbial community formation and infectious diseases. Systems biology enables the construction of complex models describing such interactions, leading to a better understanding of disease states and communities. However, before interactions between complex organisms can be understood, metabolic and energetic implications of simpler real-world host-microbe systems must be worked out. To this effect, untargeted metabolomics experiments were conducted and integrated with proteomics data to characterize key molecular-level interactions between two hyperthermophilic microbial species, both of which have reduced genomes. Metabolic changes and transfer of metabolites between the archaea Ignicoccus hospitalis and Nanoarcheum equitans were investigated using integrated LC-MS and NMR metabolomics. The study of such a system is challenging, as no genetic tools are available, growth in the laboratory is challenging, and mechanisms by which they interact are unknown. Together with information about relative enzyme levels obtained from shotgun proteomics, the metabolomics data provided useful insights into metabolic pathways and cellular networks of I. hospitalis that are impacted by the presence of N. equitans, including arginine, isoleucine, and CTP biosynthesis. On the organismal level, the data indicate that N. equitans exploits metabolites generated by I. hospitalis to satisfy its own metabolic needs. This finding is based on N. equitans's consumption of a significant fraction of the metabolite pool in I. hospitalis that cannot solely be attributed to increased biomass production for N. equitans. Combining LC-MS and NMR metabolomics datasets improved coverage of the metabolome and enhanced the identification and quantitation of cellular metabolites. PMID: 26273237 [PubMed - as supplied by publisher]

Related Articles Natural variation of plant metabolism: genetic mechanisms, interpretive caveats, evolutionary and mechanistic insights. Plant Physiol. 2015 Aug 13; Authors: Soltis NE, Kliebenstein DJ Abstract Combining quantitative genetics studies with metabolomics/metabolic profiling platforms, genomics and transcriptomics is creating significant progress in identifying the causal genes controlling natural variation in metabolite accumulations and profiles. In this review, we will discuss key mechanistic and evolutionary insights that are arising from these studies. This includes the potential role of transport and other processes in leading to a separation of the site of mechanistic causation and metabolic consequence. A re-illuminated observation is the potential for genomic variation in the organelle to alter phenotypic variation alone and in epistatic interaction with the nuclear genetic variation. These studies are also highlighting new aspects of metabolic pleiotropy both in terms of the breadth of loci altering metabolic variation as well as the potential for broader effects on plant defense regulation of the metabolic variation than has previously been predicted. We also illustrate caveats that can be overlooked when translating quantitative genetics descriptors such as heritability and per locus r2 to mechanistic or evolutionary interpretations. PMID: 26272883 [PubMed - as supplied by publisher]

Related Articles Targeted Metabolomics for Homocysteine-Related Metabolites in Primary Hepatocytes. Methods Mol Biol. 2015;1250:267-77 Authors: Selicharová I, Kořínek M Abstract Liquid chromatography-tandem mass spectrometry has become the most convenient method to identify and quantify low molecular weight metabolites from various sources. Metabolomics studies of hepatocytes hold promise for the identification of the mechanisms of toxicant-related disease processes. In this chapter, we present a rapid and sensitive liquid chromatography-tandem mass spectrometry method for the quantification of intracellular concentrations of nine homocysteine-based metabolites, namely homocysteine, methionine, cysteine, dimethylglycine, cystathionine, S-adenosylmethionine, S-adenosylhomocysteine, choline, and betaine. The method is specifically designed for the analysis of cultured primary hepatocytes. PMID: 26272149 [PubMed - in process]

Related Articles Transcriptomics of Hepatocytes Treated with Toxicants for Investigating Molecular Mechanisms Underlying Hepatotoxicity. Methods Mol Biol. 2015;1250:225-40 Authors: Shinde V, Stöber R, Nemade H, Sotiriadou I, Hescheler J, Hengstler J, Sachinidis A Abstract Transcriptomics is a powerful tool for high-throughput gene expression profiling. Transcriptome microarray experiments conducted with RNA isolated from hepatocytes after exposure to toxicants enable a deep insight into the molecular mechanisms of hepatotoxicity. This understanding, along with structure-activity relationships underlying hepatotoxicity, will provide a novel strategy to design cost-effective and safer therapeutics. Transcriptomics studies conducted with established hepatotoxic drugs in various in vitro and in vivo hepatotoxicity test systems have contributed to the elucidation of the mechanistic basis of liver insults, which were later on substantiated at the proteomics and metabolomics levels. The present chapter is focused on comprehensive transcriptomics of cultured primary hepatocytes treated with chemicals by applying Affymetrix microarray technology. It also describes the detailed protocol for culturing of hepatocytes, their exposure to toxicants as well as sample collection, including RNA isolation, RNA target preparation and finally the hybridization to gene chips for microarray expression analysis. PMID: 26272146 [PubMed - in process]

Related Articles Red blood cell storage in additive solution-7 preserves energy and redox metabolism: a metabolomics approach. Transfusion. 2015 Aug 14; Authors: D'Alessandro A, Nemkov T, Hansen KC, Szczepiorkowski ZM, Dumont LJ Abstract BACKGROUND: Storage and transfusion of red blood cells (RBCs) has a huge medical and economic impact. Routine storage practices can be ameliorated through the implementation of novel additive solutions (ASs) that tackle the accumulation of biochemical and morphologic lesion during routine cold liquid storage in the blood bank, such as the recently introduced alkaline solution AS-7. Here we hypothesize that AS-7 might exert its beneficial effects through metabolic modulation during routine storage. STUDY DESIGN AND METHODS: Apheresis RBCs were resuspended either in control AS-3 or experimental AS-7, before ultrahigh-performance liquid chromatography-mass spectrometry metabolomics analysis. RESULTS: Unambiguous assignment and relative quantitation was achieved for 229 metabolites. AS-3 and AS-7 results in many similar metabolic trends over storage, with AS-7 RBCs being more metabolically active in the first storage week. AS-7 units had faster fueling of the pentose phosphate pathway, higher total glutathione pools, and increased flux through glycolysis as indicated by higher levels of pathway intermediates. Metabolite differences are especially observed at 7 days of storage, but were still maintained throughout 42 days. CONCLUSION: AS-7 formulation (chloride free and bicarbonate loading) appears to improve energy and redox metabolism in stored RBCs in the early storage period, and the differences, though diminished, are still appreciable by Day 42. Energy metabolism and free fatty acids should be investigated as potentially important determinants for preservation of RBC structure and function. Future studies will be aimed at identifying metabolites that correlate with in vitro and in vivo circulation times. PMID: 26271632 [PubMed - as supplied by publisher]

Related Articles Type 2 diabetes is associated with postprandial amino acid measures. Arch Biochem Biophys. 2015 Aug 10; Authors: Mook-Kanamori DO, de Mutsert R, Rensen PC, Prehn C, Adamski J, Heijer MD, le Cessie S, Suhre K, Rosendaal FR, Willems van Dijk K Abstract Most studies examining the association between type 2 diabetes (T2D) and amino acids have focused on fasting concentrations. We hypothesized that, besides fasting concentrations, amino acid responses to a standardized meal challenge are also associated with T2D. In a cross-sectional study of 525 participants (165 newly-diagnosed T2D, 186 newly-diagnosed impaired fasting glycaemia, and 174 normal fasting glucose), we examined postprandial amino acid concentrations and the responses (defined as the concentrations and responses 150 minutes after a standardized meal) of fourteen amino acids in relation to T2D. T2D was associated with lower postprandial concentration of seven amino acids compared to the normal fasting glucose group (lowest effect estimate for serine: -0.54 standard deviations (SD) (95% CI: -0.77, -0.32)), and higher concentrations of phenylalanine, tryptophan, tyrosine and (iso-)leucine (highest effect estimate for (iso-)leucine: 0.44 SD (95% CI: 0.20, 0.67)). Regarding the meal responses, T2D was associated with lower responses of seven amino acids (ranging from -0.55 SD ((95% CI): -0.78, -0.33) for serine to -0.25 SD ((95% CI: 0.-0.45, -0.02) for ornithine). We conclude that T2D is associated with postprandial concentrations of amino acids and a reduced amino acid meal response, indicating that these measures may also be potential markers of T2D. PMID: 26271442 [PubMed - as supplied by publisher]

Related Articles Serum Lipid and Serum Metabolite Components in relation to anthropometric parameters in EPIC-Potsdam participants. Metabolism. 2015 Jul 11; Authors: Foerster J, Hyötyläinen T, Oresic M, Nygren H, Boeing H Abstract BACKGROUND/AIM: Lipidomic and metabolomic techniques become more and more important in human health research. Recent developments in analytical techniques enable the investigation of high amounts of substances. The high numbers of metabolites and lipids that are detected with among others mass spectrometric techniques challenge in most cases the statistical processes to bring out stable and interpretable results. This study targets to use the novel non-established statistical method treelet transform (TT) to investigate high numbers of metabolites and lipids and to compare the results with the established method principal component analysis (PCA). Serum lipid and metabolite profiles are investigated regarding their association to anthropometric parameters associated to obesity. METHODS: From 226 participants of the EPIC (European Prospective Investigation into Cancer and Nutrition)-Potsdam study blood samples were investigated with an untargeted metabolomics approach regarding serum metabolites and lipids. Additionally, participants were surveyed anthropometrically to assess parameters of obesity, such as body mass index (BMI), waist-to-hip-ratio (WHR) and body fat mass. TT and PCA are used to generate treelet components (TCs) and factors summarizing serum metabolites and lipids in new, latent variables without too much loss of information. With partial correlations TCs and factors were associated to anthropometry under the control for relevant parameters, such as sex and age. RESULTS: TT with metabolite variables (p=121) resulted in 5 stable and interpretable TCs explaining 18.9% of the variance within the data. PCA on the same variables generated 4 quite complex, less easily interpretable factors explaining 37.5% of the variance. TT on lipidomic data (p=353) produced 3 TCs as well as PCA on the same data resulted in 3 factors; the proportion of explained variance was 17.8% for TT and 39.8% for PCA. In both investigations TT ended up with stable components that are easier to interpret than the factors from the PCA. In general, the generated TCs and factors were similar in their structure when the factors are considered regarding the original variables loading high on them. Both TCs and factors showed associations to anthropometric measures. CONCLUSIONS: TT is a suitable statistical method to generate summarizing, latent variables in data sets with more variables than observations. In the present investigation it resulted in similar latent variables compared to the established method of PCA. Whereby less variance is explained by the summarizing constructs of TT compared to the factors of PCA, TCs are easier to interpret. Additionally the resulting TCs are quite stable in bootstrap samples. PMID: 26271139 [PubMed - as supplied by publisher]

Related Articles Serum metabonomic analysis of apoE(-/-) mice reveals progression axes for atherosclerosis based on NMR spectroscopy. Mol Biosyst. 2014 Dec;10(12):3170-8 Authors: Yang Y, Liu Y, Zheng L, Wu T, Li J, Zhang Q, Li X, Yuan F, Wang L, Guo J Abstract Atherosclerosis is a multifactorial and progressive disease commonly correlated with a high fat diet. The aim of this study was to identify potential biomarkers for the early diagnosis and monitoring of the progression of atherogenesis in apoE(-/-) mice using (1)H NMR-based metabonomics. The apoE(-/-) mice were split into four groups according to the duration of high fat feeding (0 w, 2 w, 4 w and 8 w), and each group possessed different pathological characteristics. Serum (1)H NMR-based metabonomics selectively captured the metabotypes that correlated with the degree of atherosclerosis, showing a time-dependent progression from the physiological to pathophysiological status. It was noted that changes in HDL, choline, taurine, glycine and glucose may be regarded as specific biomarkers of the early stage of atherosclerosis. With the progression of atherosclerosis, disorders in the metabolism of amino acids such as valine, alanine and methionine appeared when large atherosclerotic plaques existed. Multiple biochemical disorders involving lipid metabolism, energy and fatty acid metabolism were observed in the progression of atherosclerosis in apoE(-/-) mice. This study demonstrated that (1)H NMR-based metabonomics can provide biochemical information about the progression of atherogenesis and offer a non-invasive means to discover potential biomarkers for the onset and development of atherosclerosis. PMID: 25241798 [PubMed - indexed for MEDLINE]

Related Articles Phosphoproteomic profiling reveals IL6-mediated paracrine signaling within the Ewing sarcoma family of tumors. Mol Cancer Res. 2014 Dec;12(12):1740-54 Authors: Anderson JL, Titz B, Akiyama R, Komisopoulou E, Park A, Tap WD, Graeber TG, Denny CT Abstract UNLABELLED: Members of the Ewing sarcoma family of tumors (ESFT) contain tumor-associated translocations that give rise to oncogenic transcription factors, most commonly EWS/FLI1. EWS/FLI1 plays a dominant role in tumor progression by modulating the expression of hundreds of target genes. Here, the impact of EWS/FLI1 inhibition, by RNAi-mediated knockdown, on cellular signaling was investigated using mass spectrometry-based phosphoproteomics to quantify global changes in phosphorylation. This unbiased approach identified hundreds of unique phosphopeptides enriched in processes such as regulation of cell cycle and cytoskeleton organization. In particular, phosphotyrosine profiling revealed a large upregulation of STAT3 phosphorylation upon EWS/FLI1 knockdown. However, single-cell analysis demonstrated that this was not a cell-autonomous effect of EWS/FLI1 deficiency, but rather a signaling effect occurring in cells in which knockdown does not occur. Conditioned media from knockdown cells were sufficient to induce STAT3 phosphorylation in control cells, verifying the presence of a soluble factor that can activate STAT3. Cytokine analysis and ligand/receptor inhibition experiments determined that this activation occurred, in part, through an IL6-dependent mechanism. Taken together, the data support a model in which EWS/FLI1 deficiency results in the secretion of soluble factors, such as IL6, which activate STAT signaling in bystander cells that maintain EWS/FLI1 expression. Furthermore, these soluble factors were shown to protect against apoptosis. IMPLICATIONS: EWS/FLI1 inhibition results in a novel adaptive response and suggests that targeting the IL6/STAT3 signaling pathway may increase the efficacy of ESFT therapies. PMID: 25092916 [PubMed - indexed for MEDLINE]