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Dorothea Lesche Roland Geyer Daniel Lienhard Christos T. Nakas Gaëlle Diserens Peter Vermathen Alexander B. Leichtle 《Metabolomics : Official journal of the Metabolomic Society》2016,12(10):159
Background
Centrifugation is an indispensable procedure for plasma sample preparation, but applied conditions can vary between labs.Aim
Determine whether routinely used plasma centrifugation protocols (1500×g 10 min; 3000×g 5 min) influence non-targeted metabolomic analyses.Methods
Nuclear magnetic resonance spectroscopy (NMR) and High Resolution Mass Spectrometry (HRMS) data were evaluated with sparse partial least squares discriminant analyses and compared with cell count measurements.Results
Besides significant differences in platelet count, we identified substantial alterations in NMR and HRMS data related to the different centrifugation protocols.Conclusion
Already minor differences in plasma centrifugation can significantly influence metabolomic patterns and potentially bias metabolomics studies.3.
Background
Recently, measuring phenotype similarity began to play an important role in disease diagnosis. Researchers have begun to pay attention to develop phenotype similarity measurement. However, existing methods ignore the interactions between phenotype-associated proteins, which may lead to inaccurate phenotype similarity.Results
We proposed a network-based method PhenoNet to calculate the similarity between phenotypes. We localized phenotypes in the network and calculated the similarity between phenotype-associated modules by modeling both the inter- and intra-similarity.Conclusions
PhenoNet was evaluated on two independent evaluation datasets: gene ontology and gene expression data. The result shows that PhenoNet performs better than the state-of-art methods on all evaluation tests.4.
Thijs Welle Anna T. Hoekstra Ineke A. J. J. M. Daemen Celia R. Berkers Matheus O. Costa 《Metabolomics : Official journal of the Metabolomic Society》2017,13(7):83
Introduction
Swine dysentery caused by Brachyspira hyodysenteriae is a production limiting disease in pig farming. Currently antimicrobial therapy is the only treatment and control method available.Objective
The aim of this study was to characterize the metabolic response of porcine colon explants to infection by B. hyodysenteriae.Methods
Porcine colon explants exposed to B. hyodysenteriae were analyzed for histopathological, metabolic and pro-inflammatory gene expression changes.Results
Significant epithelial necrosis, increased levels of l-citrulline and IL-1α were observed on explants infected with B. hyodysenteriae.Conclusions
The spirochete induces necrosis in vitro likely through an inflammatory process mediated by IL-1α and NO.5.
Florian Buettner Kyle Jay Harry Wischnewski Thomas Stadelmann Shady Saad Konstantins Jefimovs Madina Mansurova Juan Gerez Claus M. Azzalin Reinhard Dechant Alfredo J. Ibáñez 《Metabolomics : Official journal of the Metabolomic Society》2017,13(5):53
Introduction
The alternative lengthening of telomeres (ALT) mechanism was first observed in the model organism S. cerevisiae. Interestingly, this mechanism is necessary for the viability of some tumor cells. Unfortunately, its molecular underpinnings are not yet completely understood.Objective
Here, we combine carefully designed non-targeted mass spectrometry-based metabolomics experiments with a bioinformatics approach to characterize the ALT positive phenotype observed in yeast at the metabolomics level.Methods
We profiled the metabolome using mass spectrometry in yeast strains that have lost telomerase expression, as well as that in pre-senescence and the rescued states. To dissect unwanted technical variation from biologically relevant variation between these states, we used a two-step normalization strategy, i.e., first, an empirical Bayesian framework; and next, we corrected for second-order technical effects.Results
Our results show that ALT-positive yeast strains present two different types of metabolic responses to the genetically-induced telomerase dysfunction: (i) systemic and (ii) specific. The key-difference between these responses is that the systemic response lasts even after the yeast strains have been genetically rescued, while the specific response does not. Interestingly, these metabolic changes can be associated with generic stress responses (e.g., DNA damage) as well as specific responses like accelerated aging of early telomerase-inactivation.Conclusions
A mass spectrometry-based metabolomics approach reveals two distinct types of metabolomics response to telomerase dysfunction in yeast. By identifying these changes in protein (e.g., ARG7, and ARG1), and metabolite (e.g., dATP, and dDTP) amounts, we complement the available information on ALT at the genome-wide level.6.
Phan Nguyen Thuy An Masamitsu Yamaguchi Eiichiro Fukusaki 《Metabolomics : Official journal of the Metabolomic Society》2017,13(3):29
Introduction
Metamorphosis is a complicated process in which cell proliferation, differentiation, and death are orchestrated to form the mature structures of insects. In Drosophila, this process is controlled by ecdysone, a steroid hormone responsible for tissue remodeling and organogenesis that gives rise to the adult fly.Objective
By using a metabolomics approach, this study aimed to elucidate global changes in the central metabolic pathways in Drosophila throughout metamorphosis and then further examine the effects of temperature and origin on metabolic profiles.Methods
Targeted and non-targeted metabolic profiling of time-course samples from Drosophila were constructed to cover a wide range of cellular metabolites during metamorphosis.Results
This was the first wide-scale metabolomics study of Drosophila metamorphosis focusing on central metabolism. The abundance of detected metabolites changed drastically and correlated strongly with the development of Drosophila pupae. In non-stress conditions, temperature affected the developmental time, but the metabolic state at a certain stage of metamorphosis remained stable. Between D. melanogaster Canton S and Oregon R, similar metabolic profiles throughout metamorphosis was observed. However, there were still differences in purine and pyrimidine metabolism at an early stage in the pupal period, which was matched by differences in ecdysteroid levels.Conclusion
This study supported the strength of metabolomics in the field of developmental biology. The results provided a general view on the metabolic profile of Drosophila during metamorphosis, which provides basic 3 knowledge for future metabolomics studies using Drosophila.7.
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Nicholas J. Bond Albert Koulman Julian L. Griffin Zoe Hall 《Metabolomics : Official journal of the Metabolomic Society》2017,13(11):128
Introduction
Mass spectrometry imaging (MSI) experiments result in complex multi-dimensional datasets, which require specialist data analysis tools.Objectives
We have developed massPix—an R package for analysing and interpreting data from MSI of lipids in tissue.Methods
massPix produces single ion images, performs multivariate statistics and provides putative lipid annotations based on accurate mass matching against generated lipid libraries.Results
Classification of tissue regions with high spectral similarly can be carried out by principal components analysis (PCA) or k-means clustering.Conclusion
massPix is an open-source tool for the analysis and statistical interpretation of MSI data, and is particularly useful for lipidomics applications.9.
Qiong Xu Chun-yang Li Yi Wang Hui-ping Li Bing-bing Wu Yong-hui Jiang 《BMC medical genomics》2018,11(1):92
Background
Verheij syndrome is a rare microdeletion syndrome of chromosome 8q24.3 that harbors PUF60, SCRIB, and NRBP2 genes. Subsequently, loss of function mutations in PUF60 have been found in children with clinical features significantly overlapping with Verheij.Case presentation
Here we present the first Chinese Han patient with a de novo nonsense variant (c.1357C?>?T, p.Gln453*) in PUF60 by clinical whole exome sequencing. The 5-year-old boy presents with dysmorphic facial features, intellectual disability, and growth retardation but without apparent cardiac, renal, ocular, and spinal anomalies.Conclusions
Our finding contributes to the understanding of the genotype and phenotype in PUF60 related disorder.10.
Korey J. Brownstein Mahmoud Gargouri William R. Folk David R. Gang 《Metabolomics : Official journal of the Metabolomic Society》2017,13(11):133
Introduction
Botanicals containing iridoid and phenylethanoid/phenylpropanoid glycosides are used worldwide for the treatment of inflammatory musculoskeletal conditions that are primary causes of human years lived with disability, such as arthritis and lower back pain.Objectives
We report the analysis of candidate anti-inflammatory metabolites of several endemic Scrophularia species and Verbascum thapsus used medicinally by peoples of North America.Methods
Leaves, stems, and roots were analyzed by ultra-performance liquid chromatography-mass spectrometry (UPLC-MS) and partial least squares-discriminant analysis (PLS-DA) was performed in MetaboAnalyst 3.0 after processing the datasets in Progenesis QI.Results
Comparison of the datasets revealed significant and differential accumulation of iridoid and phenylethanoid/phenylpropanoid glycosides in the tissues of the endemic Scrophularia species and Verbascum thapsus.Conclusions
Our investigation identified several species of pharmacological interest as good sources for harpagoside and other important anti-inflammatory metabolites.11.
Background
Interferon induced transmembrane protein 3 (IFITM3) is transcribed in most tissues and highly interferon-inducible. However, the role of IFITM3 in cancer is still poorly understood.Methods
Expression levels ofIFITM3were analyzed in 60 glioma patients by immunohistochemistry (IHC). Following closely, we investigated the phenotype of IFITM3 knockdown on glioma cell growth and tumorigenesis in vitro using lentivirus-mediated loss-of-function strategy.Results
Depletion of IFITM3in U251 cells dramatically inhibited cell proliferation and colony formation, which demonstrated that reduced IFITM3 protein levels could cause inhibition of tumorigenesis. Knockdown of IFITM3 also induced cell cycle arrest in G0/G1 phase, especially in the sub-G1 phase representing apoptotic cells. In addition, the migration of U251 cells was visibly weakened after IFITM3 knockdown, as determined by Transwell assay.Conclusions
Our findings provide new evidence that IFITM3 plays an important role in glioma cell growth and migration, suggesting that silencing of IFITM3 by RNA interference (RNAi) may be a potential approach to suppress glioma growth.12.
Zhengling Liu Zengyan Wang Changhong Hao Yonghui Tian Jingjing Fu 《Reproductive biology and endocrinology : RB&E》2018,16(1):120
Background
Whether adiponectin (ADIPOQ) polymorphisms are associated with the risk of polycystic ovary syndrome (PCOS) remain controversial. Therefore, we performed this study to better explore correlations between ADIPOQ polymorphisms and PCOS risk.Methods
Literature retrieve was conducted in PubMed, Medline and Embase. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated.Results
Eighteen studies were enrolled for analyses. Pooled overall analyses showed that rs1501299 polymorphism was significantly associated with PCOS risk (recessive model: p?=?0.02, OR?=?0.77, 95%CI 0.62–0.95; allele model: p?=?0.001, OR?=?1.15, 95%CI 1.06–1.26). Further subgroup analyses according to ethnicity of participants revealed that rs1501299 and rs2241766 polymorphisms were both significantly correlated with PCOS risk in Caucasians. In addition, rs1501299 polymorphism was also significantly correlated with PCOS risk in East Asians.Conclusions
Our findings indicated that rs1501299 and rs2241766 polymorphisms might serve as genetic biomarkers of PCOS in certain ethnicities.13.
Walter Omar Draghi María Florencia Del Papa Aiko Barsch Francisco J. Albicoro Mauricio J. Lozano Alfred Pühler Karsten Niehaus Antonio Lagares 《Metabolomics : Official journal of the Metabolomic Society》2017,13(6):71
Introduction
Sinorhizobium meliloti establishes a symbiosis with Medicago species where the bacterium fixes atmospheric nitrogen for plant nutrition. To achieve a successful symbiosis, however, both partners need to withstand biotic and abiotic stresses within the soil, especially that of excess acid, to which the Medicago-Sinorhizobium symbiotic system is widely recognized as being highly sensitive.Objective
To cope with low pH, S. meliloti can undergo an acid-tolerance response (ATR(+)) that not only enables a better survival but also constitutes a more competitive phenotype for Medicago sativa nodulation under acid and neutral conditions. To characterize this phenotype, we employed metabolomics to investigate the biochemical changes operating in ATR(+) cells.Methods
A gas chromatography/mass spectrometry approach was used on S. meliloti 2011 cultures showing ATR(+) and ATR(?) phenotypes. After an univariate and multivariate statistical analysis, enzymatic activities and/or reserve carbohydrates characterizing ATR(+) phenotypes were determined.Results
Two distinctive populations were clearly defined in cultures grown in acid and neutral pH based on the metabolites present. A shift occurred in the carbon-catabolic pathways, potentially supplying NAD(P)H equivalents for use in other metabolic reactions and/or for maintaining intracellular-pH homeostasis. Furthermore, among the mechanisms related to acid resistance, the ATR(+) phenotype was also characterized by lactate production, envelope modification, and carbon-overflow metabolism.Conclusions
Acid-challenged S. meliloti exhibited several changes in different metabolic pathways that, in specific instances, could be identified and related to responses observed in other bacteria under various abiotic stresses. Some of the observed changes included modifications in the pentose-phosphate pathway (PPP), the exopolysaccharide biosynthesis, and in the myo-inositol degradation intermediates. Such modifications are part of a metabolic adaptation in the rhizobia that, as previously reported, is associated to improved phenotypes of acid tolerance and nodulation competitiveness.14.
Roman S. Popov Natalia V. Ivanchina Alla A. Kicha Timofey V. Malyarenko Boris B. Grebnev Pavel S. Dmitrenok Valentin A. Stonik 《Metabolomics : Official journal of the Metabolomic Society》2016,12(6):106
Introduction
Starfish are recognized as interesting source of natural steroid products with pharmaceutical potential. Polar steroid metabolites of starfish have unique chemical structures and exhibit various biological activities but their biological functions are controversial.Objectives
The objective of this study was to investigate the response of polar steroid metabolome of the starfish Patiria (=Asterina) pectinifera on various environmental factors and stresses.Methods
Here we first have applied MS-based environmental metabolomics to elucidate the metabolic changes of polar steroid metabolome of starfish. Using HPLC–ESI–Q/TOF–MS approach followed by statistical analysis including principal component analysis and partial least squares discriminant analysis for data classification and potential biomarkers selection, we investigated the changes induced by feeding, injury, variations in water temperature and salinity, and oxygen deficiency.Results
According to multivariate and univariate statistical analysis the responses to feeding, injury and water heating were better expressed than the others and have some similarity in their action on the steroid metabolome of the starfish P. pectinifera. Most constituents of asterosaponin pool were reduced and most constituents of polyhydroxysteroid and related glycoside pool were increased at that.Conclusion
Our results indicate that various metabolic changes in polar steroid constituents of P. pectinifera are induced by feeding and stresses. We believe that these responses are connected with biological multifunctionality of these compounds.15.
16.
Hyun-Soo Kim 《Biotechnology letters》2016,38(11):1955-1960
Objective
To identify a novel gene responsible for organic solvent-tolerance by screening a transposon-mediated deletion mutant library based on Saccharomyces cerevisiae L3262.Results
One strain tolerant of up to 0.5 % (v/v) n-hexane and cyclohexane was isolated. The determination of transposon insertion site identified one gene, YLR162W, and revealed disruption of the ORF of this gene, indicating that organic solvent tolerance can be conferred. Such a tolerant phenotype reverted to the sensitive phenotype on the autologous or overexpression of this gene. This transposon mutant grew faster than the control strain when cultured at 30 °C in YPD medium containing 0.5 % (v/v) n-hexane and cyclohexane respectively.Conclusion
Disruption of YLR162W in S. cerevisiae results in increased tolerance to organic solvents.17.
Lai-Fang Zhou Bo-Wen Zhao Ning-Nan Guan Wei-Min Wang Ze-Xia Gao 《Metabolomics : Official journal of the Metabolomic Society》2017,13(4):40
Introduction
In some fish species, it is difficult to distinguish mature females from immature females or females that have already spawned via appearance or other convenient methods. Few studies have investigated plasma metabolite profiling for the prediction of fish maturation.Objectives
We investigated the comprehensive metabolic profiles of plasma among immature females and mature females ready to spawn, as well as already spawned breeders of blunt snout bream (Megalobrama amblycephala). The purpose of this study was to screen out potential biomarkers for sexually mature female M. amblycephala compared to immature female individuals and already spawned breeders.Methods
Three groups were set up in this study, which included 1-year-old immature females, 2-year-old sexually mature females ready to spawn and successfully spawned females of M. amblycephala. Plasma samples were collected to investigate comprehensive metabolic profiles through UPLC-MS/MS based on a metabolomics analysis method.Results
According to multivariate and univariate statistical analysis, plasma metabolite profiles of the three groups were clearly separated. The differential plasma metabolites from three hormone related pathways including the GnRH signaling pathway, steroid hormone biosynthesis and steroid biosynthesis, were analyzed. A total of 29 metabolites were identified as differential biomarkers associated with the female maturation status.Conclusion
The identified potential biomarkers could be useful in separating mature M. amblycephala from immature individuals or ovulation-induced female individuals, which would allow for more effective artificial breeding. The results may contribute to a better understanding of the maturation mechanisms of fish in the aspect of metabolomics.18.
Elba Garreta-Lara Bruno Campos Carlos Barata Silvia Lacorte Romà Tauler 《Metabolomics : Official journal of the Metabolomic Society》2016,12(5):86
Introduction
Climate change is a major concern for the scientific community, demanding novel information about the effects of environmental stressors on living organisms. Metabolic profiling is required for achieving the most extensive possible range of compounds and their concentration changes on stressed conditions.Objectives
Individuals of the crustacean species Daphnia magna were exposed to three different abiotic factors linked to global climate change: high salinity, high temperature levels and hypoxia. Advanced chemometric tools were used to characterize the metabolites affected by the exposure.Method
An exploratory analysis of gas chromatography-mass spectrometry (GC–MS) data was performed to discriminate between control and exposed daphnid samples. Due to the complexity of these GC–MS data sets, a comprehensive untargeted analysis of the full scan data was performed using multivariate curve resolution-alternating least squares (MCR-ALS) method. This approach enabled to resolve most of the metabolite signals from interference peaks caused by derivatization reactions. Metabolites with significant changes in their peak areas were tentatively identified and the involved metabolic pathways explored.Results
D. magna metabolic biomarkers are proposed for the considered physical factors. Metabolites related with energy metabolic pathways including some amino acids, carbohydrates, organic acids and nucleosides were identified as potential biomarkers of the investigated treatments.Conclusions
The proposed untargeted GC–MS metabolomics strategy and multivariate data analysis tools were useful to investigate D. magna metabolome under environmental stressed conditions.19.
Zexi Cai Trine Michelle Villumsen Torben Asp Bernt Guldbrandtsen Goutam Sahana Mogens Sandø Lund 《BMC genetics》2018,19(1):103
Background
Identification of genes underlying production traits is a key aim of the mink research community. Recent availability of genomic tools have opened the possibility for faster genetic progress in mink breeding. Availability of mink genome assembly allows genome-wide association studies in mink.Results
In this study, we used genotyping-by-sequencing to obtain single nucleotide polymorphism (SNP) genotypes of 2496 mink. After multiple rounds of filtering, we retained 28,336 high quality SNPs and 2352 individuals for a genome-wide association study (GWAS). We performed the first GWAS for body weight, behavior, along with 10 traits related to fur quality in mink.Conclusions
Combining association results with existing functional information of genes and mammalian phenotype databases, we proposed WWC3, MAP2K4, SLC7A1 and USP22 as candidate genes for body weight and pelt length in mink.20.
Ying-ge Wang Jin-mei Cheng Hai-bo Ding Xi Lin Guo-hao Chen Mei Zhou Sheng-nan Ye 《Mycopathologia》2018,183(3):551-558