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: 1 hour 34 min ago

The omics approach to bee nutritional landscape.

Sat, 21/09/2019 - 12:21
Related Articles The omics approach to bee nutritional landscape. Metabolomics. 2019 Sep 20;15(10):127 Authors: Chakrabarti P, Morré JT, Lucas HM, Maier CS, Sagili RR Abstract BACKGROUND: Significant annual honey bee colony losses have been reported in the USA and across the world over the past years. Malnutrition is one among several causative factors for such declines. Optimal nutrition serves as the first line of defense against multiple stressors such as parasites/pathogens and pesticides. Given the importance of nutrition, it is imperative to understand bee nutrition holistically, identifying dietary sources that may fulfill bee nutritional needs. Pollen is the primary source of protein for bees and is critical for brood rearing and colony growth. Currently, there is significant gap in knowledge regarding the chemical and nutritional composition of pollen. METHODS: Targeted sterol analysis and untargeted metabolomics were conducted on five commercially available crop pollens, three bee-collected crop pollens, three vegetable oils (often added to artificial protein supplements by beekeepers), and one commonly used artificial protein supplement. RESULTS: This study reports key phytosterols and metabolites present across a spectrum of bee diets, including some of the major bee-pollinated crop pollens in the western United States. Significant differences were observed in sterol concentrations among the dietary sources tested. Among all quantified sterols, the highest concentrations were observed for 24-methylenecholesterol and further, pollen samples exhibited the highest 24-methylenecholesterol among all diet sources that were tested. Also, 236 metabolites were identified across all dietary sources examined. CONCLUSION: Information gleaned from this study is crucial in understanding the nutritional landscape available to all bee pollinators and may further assist in future efforts to develop comprehensive database of nutrients and metabolites present in all bee diets. PMID: 31538263 [PubMed - in process]

MDH1 deficiency is a metabolic disorder of the malate-aspartate shuttle associated with early onset severe encephalopathy.

Sat, 21/09/2019 - 12:21
Related Articles MDH1 deficiency is a metabolic disorder of the malate-aspartate shuttle associated with early onset severe encephalopathy. Hum Genet. 2019 Sep 19;: Authors: Broeks MH, Shamseldin HE, Alhashem A, Hashem M, Abdulwahab F, Alshedi T, Alobaid I, Zwartkruis F, Westland D, Fuchs S, Verhoeven-Duif NM, Jans JJM, Alkuraya FS Abstract The reversible oxidation of L-malate to oxaloacetate is catalyzed by NAD(H)-dependent malate dehydrogenase (MDH). MDH plays essential roles in the malate-aspartate shuttle and the tricarboxylic acid cycle. These metabolic processes are important in mitochondrial NADH supply for oxidative phosphorylation. Recently, bi-allelic mutations in mitochondrial MDH2 were identified in patients with global developmental delay, epilepsy and lactic acidosis. We now report two patients from an extended consanguineous family with a deleterious variant in the cytosolic isoenzyme of MDH (MDH1). The homozygous missense variant in the NAD+-binding domain of MDH1 led to severely diminished MDH protein expression. The patients presented with global developmental delay, epilepsy and progressive microcephaly. Both patients had normal concentrations of plasma amino acids, acylcarnitines, lactate, and urine organic acids. To identify the metabolic consequences of MDH1 deficiency, untargeted metabolomics was performed on dried blood spots (DBS) from the patients and in MDH1 knockout HEK293 cells that were generated by Crispr/Cas9. Increased levels of glutamate and glycerol-3-phosphate were found in DBS of both patients. In MDH1 KO HEK293 cells, increased levels of glycerol-3-phosphate were also observed, as well as increased levels of aspartate and decreased levels of fumarate. The consistent finding of increased concentrations of glycerol-3-phosphate may represent a compensatory mechanism to enhance cytosolic oxidation of NADH by the glycerol-P-shuttle. In conclusion, MDH1 deficiency is a new metabolic defect in the malate-aspartate shuttle characterized by a severe neurodevelopmental phenotype with elevated concentrations of glycerol-3-phosphate as a potential biomarker. PMID: 31538237 [PubMed - as supplied by publisher]

Biobanking for discovery of novel cardiovascular biomarkers using imaging-quantified disease burden: protocol for the longitudinal, prospective, BioHEART-CT cohort study.

Sat, 21/09/2019 - 12:21
Related Articles Biobanking for discovery of novel cardiovascular biomarkers using imaging-quantified disease burden: protocol for the longitudinal, prospective, BioHEART-CT cohort study. BMJ Open. 2019 Sep 18;9(9):e028649 Authors: Kott KA, Vernon ST, Hansen T, Yu C, Bubb KJ, Coffey S, Sullivan D, Yang J, O'Sullivan J, Chow C, Patel S, Chong J, Celermajer DS, Kritharides L, Grieve SM, Figtree GA Abstract INTRODUCTION: Coronary artery disease (CAD) persists as a major cause of morbidity and mortality worldwide despite intensive identification and treatment of traditional risk factors. Data emerging over the past decade show a quarter of patients have disease in the absence of any known risk factor, and half have only one risk factor. Improvements in quantification and characterisation of coronary atherosclerosis by CT coronary angiography (CTCA) can provide quantitative measures of subclinical atherosclerosis-enhancing the power of unbiased 'omics' studies to unravel the missing biology of personal susceptibility, identify new biomarkers for early diagnosis and to suggest new targeted therapeutics. METHODS AND ANALYSIS: BioHEART-CT is a longitudinal, prospective cohort study, aiming to recruit 5000 adult patients undergoing clinically indicated CTCA. After informed consent, patient data, blood samples and CTCA imaging data are recorded. Follow-up for all patients is conducted 1 month after recruitment, and then annually for the life of the study. CTCA data provide volumetric quantification of total calcified and non-calcified plaque, which will be assessed using established and novel scoring systems. Comprehensive molecular phenotyping will be performed using state-of-the-art genomics, metabolomics, proteomics and immunophenotyping. Complex network and machine learning approaches will be applied to biological and clinical datasets to identify novel pathophysiological pathways and to prioritise new biomarkers. Discovery analysis will be performed in the first 1000 patients of BioHEART-CT, with validation analysis in the following 4000 patients. Outcome data will be used to build improved risk models for CAD. ETHICS AND DISSEMINATION: The study protocol has been approved by the human research ethics committee of North Shore Local Health District in Sydney, Australia. All findings will be published in peer-reviewed journals or at scientific conferences. TRIAL REGISTRATION NUMBER: ACTRN12618001322224. PMID: 31537558 [PubMed - in process]

Metabolomics Identifies a Biomarker Revealing in Vivo Loss of Functional ß-Cell Mass Before Diabetes Onset.

Sat, 21/09/2019 - 12:21
Related Articles Metabolomics Identifies a Biomarker Revealing in Vivo Loss of Functional ß-Cell Mass Before Diabetes Onset. Diabetes. 2019 Sep 19;: Authors: Li L, Krznar P, Erban A, Agazzi A, Martin-Levilain J, Supale S, Kopka J, Zamboni N, Maechler P Abstract Identification of pre-diabetic individuals with decreased functional ß-cell mass is essential for the prevention of diabetes. However, in vivo detection of early asymptomatic ß-cell defect remains unsuccessful. Metabolomics emerged as a powerful tool in providing read-outs of early disease states before clinical manifestation. We aimed at identifying novel plasma biomarkers for loss of functional ß-cell mass in the asymptomatic pre-diabetic stage. Non-targeted and targeted metabolomics were applied on both lean ß-Phb2-/- mice (ß-cell-specific prohibitin-2 knockout) and obese db/db mice (leptin receptor mutant), two distinct mouse models requiring neither chemical nor diet treatments to induce spontaneous decline of functional ß-cell mass promoting progressive diabetes development. Non-targeted metabolomics on ß-Phb2-/- mice identified 48 and 82 significantly affected metabolites in liver and plasma, respectively. Machine learning analysis pointed to deoxyhexose sugars consistently reduced at the asymptomatic pre-diabetic stage, including in db/db mice, showing strong correlation with the gradual loss of ß-cells. Further targeted metabolomics by GC-MS uncovered the identity of the deoxyhexose with 1,5-anhydroglucitol displaying the most significant changes. In conclusion, this study identified 1,5-anhydroglucitol associated with the loss of functional ß-cell mass and uncovered metabolic similarities between liver and plasma, providing insights into the systemic effects caused by early decline in ß-cells. PMID: 31537525 [PubMed - as supplied by publisher]

Comparison of metabolic profiles of yeasts based on the difference of the Crabtree positive and negative.

Sat, 21/09/2019 - 12:21
Related Articles Comparison of metabolic profiles of yeasts based on the difference of the Crabtree positive and negative. J Biosci Bioeng. 2019 Sep 16;: Authors: Imura M, Nitta K, Iwakiri R, Matsuda F, Shimizu H, Fukusaki E Abstract The Crabtree effect involves energy management in which yeasts utilize glycolysis as the terminal electron acceptor instead of oxygen, despite the presence of sufficient dissolved oxygen, when oxygen concentrations exceed a certain limit. The Crabtree effect is detrimental to bakery yeast production, because it results in lower cellular glucose yields. Batch culture of Saccharomyces cerevisiae, a Crabtree positive yeast, decreased the cell yield of glucose and produced large amounts of ethanol despite a high specific glucose consumption rate compared to Candida utilis, a Crabtree negative yeast. This study investigated the effect of these characteristics on metabolite levels. We performed metabolome analysis of both yeasts during each growth phase of batch culture using liquid chromatography-tandem mass spectrometry and gas chromatography-mass spectrometry. Principle component analysis of metabolome data indicated that the Crabtree effect affected metabolites related to NADH synthesis in central metabolism. The amount of these metabolites in S. cerevisiae was lower than that in C. utilis. However, to maintain the specific glucose consumption rate at high levels, yeasts must avoid depletion of NAD+, which is essential for glucose utilization. Our results indicated that NADH was oxidized by converting acetaldehyde to ethanol in S. cerevisiae, which is in accordance with previous reports. Therefore, the specific NADH production rates of S. cerevisiae and C. utilis did not show a difference. This study suggested that NAD+/NADH ratio is disrupted by the Crabtree effect, which in turn influenced central metabolism and that S. cerevisiae maintained the NAD+/NADH ratio by producing ethanol. PMID: 31537452 [PubMed - as supplied by publisher]

Characterization of the cold and hot natures of raw and processed Rehmanniae Radix by integrated metabolomics and network pharmacology.

Sat, 21/09/2019 - 12:21
Related Articles Characterization of the cold and hot natures of raw and processed Rehmanniae Radix by integrated metabolomics and network pharmacology. Phytomedicine. 2019 Aug 21;:153071 Authors: Xia F, Liu C, Wan JB Abstract BACKGROUND: The processing of Chinese materia medica (CMM) is one of the characteristics and advantages of traditional Chinese medicine (TCM). Occasionally, the processing of CMM might reverse the cold/hot nature of CMM. For example, the nature of raw Rehmanniae Radix (RR) is cool, while the processed Rehmanniae Radix (PR) by steaming is hot. Because the cold/hot nature of CMM is defined by the body's response to CMMs, a metabolomics approach, allowing the monitoring of the fluctuation of endogenous metabolites related to an exogenous stimulus, might be an ideal tool to uncover the cold/hot nature of different forms of Rehmanniae Radix. PURPOSE: An integrated strategy combining metabolomics and network pharmacology was applied to illuminate the different natures of raw and processed Rehmanniae Radix. STUDY DESIGN: Mice were orally administered RR and PR once daily for ten days. The entire metabolic changes in the plasma of mice were profiled by ultra-high performance liquid chromatography/quadrupole time-of-flight mass spectrometry (UHPLC/Q-TOF MS). Furthermore, network pharmacology analysis was performed to identify the underlying targets related to iridoids that significantly changed during the processing. RESULTS: The metabolomics analysis results demonstrated a clear separation of the metabolic phenotypes among the control, RR and two PR groups in both the positive and negative modes. Nine lysophosphatidylcholines (LysoPCs), LysoPC (16:0), LysoPC (18:2), LysoPC (18:1), LysoPC (22:6), LysoPC (20:2), LysoPC (18:0), LysoPC (16:1), LysoPC (20:4) and LysoPC (20:5), that decreased in the RR-treated group, but increased in the PR-treated group, were identified to be potential biomarkers related to the natures of RR and PR. The network pharmacology results indicated that four iridoids in Rehmanniae Radix, 8-epiloganic acid, 6-O-p-coumaroyl ajugol, 6-O-p-hydroxybenzoyl ajugol and ajugol, might play important roles in the different natures of raw and processed Rehmanniae Radix. CONCLUSIONS: There might be a strong connection between the cold/hot nature of different forms of Rehmanniae Radix and LysoPC metabolism. This study offers new insight into the cold/hot nature of Rehmanniae Radix. PMID: 31537418 [PubMed - as supplied by publisher]

Biomarker Glycoprotein Acetyls Is Associated With the Risk of a Wide Spectrum of Incident Diseases and Stratifies Mortality Risk in Angiography Patients.

Sat, 21/09/2019 - 12:21
Related Articles Biomarker Glycoprotein Acetyls Is Associated With the Risk of a Wide Spectrum of Incident Diseases and Stratifies Mortality Risk in Angiography Patients. Circ Genom Precis Med. 2018 11;11(11):e002234 Authors: Kettunen J, Ritchie SC, Anufrieva O, Lyytikäinen LP, Hernesniemi J, Karhunen PJ, Kuukasjärvi P, Laurikka J, Kähönen M, Lehtimäki T, Havulinna AS, Salomaa V, Männistö S, Ala-Korpela M, Perola M, Inouye M, Würtz P Abstract BACKGROUND: Integration of systems-level biomolecular information with electronic health records has led to recent interest in the glycoprotein acetyls (GlycA) biomarker-a serum- or plasma-derived nuclear magnetic resonance spectroscopy signal that represents the abundance of circulating glycated proteins. GlycA predicts risk of diverse outcomes, including cardiovascular disease, type 2 diabetes mellitus, and all-cause mortality; however, the underlying detailed associations of GlycA's morbidity and mortality risk are currently unknown. METHODS: We used 2 population-based cohorts totaling 11 861 adults from the Finnish general population to test for an association with 468 common incident hospitalization and mortality outcomes during an 8-year follow-up. Further, we utilized 900 angiography patients to test for GlycA association with mortality risk and potential utility for mortality risk discrimination during 12-year follow-up. RESULTS: New associations with GlycA and incident alcoholic liver disease, chronic renal failure, glomerular diseases, chronic obstructive pulmonary disease, inflammatory polyarthropathies, and hypertension were uncovered, and known incident disease associations were replicated. GlycA associations for incident disease outcomes were in general not attenuated when adjusting for hsCRP (high-sensitivity C-reactive protein). Among 900 patients referred to angiography, GlycA had hazard ratios of 4.87 (95% CI, 2.45-9.65) and 5.00 (95% CI, 2.38-10.48) for 12-year risk of mortality in the fourth and fifth quintiles by GlycA levels, demonstrating its prognostic potential for identification of high-risk individuals. When modeled together, both hsCRP and GlycA were attenuated but remained significant. CONCLUSIONS: GlycA was predictive of myriad incident diseases across many major internal organs and stratified mortality risk in angiography patients. Both GlycA and hsCRP had shared and independent contributions to mortality risk, suggesting chronic inflammation as an etiological factor. GlycA may be useful in improving risk prediction in specific disease settings. PMID: 30571186 [PubMed - indexed for MEDLINE]

Anionic 1,2-distearoyl-sn-glycero-3-phosphoglycerol (DSPG) liposomes induce antigen-specific regulatory T cells and prevent atherosclerosis in mice.

Sat, 21/09/2019 - 12:21
Related Articles Anionic 1,2-distearoyl-sn-glycero-3-phosphoglycerol (DSPG) liposomes induce antigen-specific regulatory T cells and prevent atherosclerosis in mice. J Control Release. 2018 12 10;291:135-146 Authors: Benne N, van Duijn J, Lozano Vigario F, Leboux RJT, van Veelen P, Kuiper J, Jiskoot W, Slütter B Abstract Atherosclerosis is the predominant underlying pathology of many types of cardiovascular disease and is one of the leading causes of death worldwide. It is characterized by the retention of oxidized low-density lipoprotein (ox-LDL) in lipid-rich macrophages (foam cells) in the intima of arteries. Autoantigens derived from oxLDL can be used to vaccinate against atherosclerosis. However, a major challenge is the induction of antigen-specific Tregs in a safe and effective way. Here we report that liposomes containing the anionic phospholipid 1,2-distearoyl-sn-glycero-3-phosphoglycerol (DSPG) induce Tregs that are specific for the liposomes' cargo. Mechanistically, we show a crucial role for the protein corona that forms on the liposomes in the circulation, as uptake of DSPG-liposomes by antigen-presenting cells is mediated via complement component 1q (C1q) and scavenger receptors (SRs). Vaccination of atherosclerotic mice on a western-type diet with DSPG-liposomes encapsulating an LDL-derived peptide antigen significantly reduced plaque formation by 50% and stabilized the plaques, and reduced serum cholesterol concentrations. These results indicate that DSPG-liposomes have potential as a delivery system in vaccination against atherosclerosis. PMID: 30365993 [PubMed - indexed for MEDLINE]

BASIS: High-performance bioinformatics platform for processing of large-scale mass spectrometry imaging data in chemically augmented histology.

Sat, 21/09/2019 - 12:21
Related Articles BASIS: High-performance bioinformatics platform for processing of large-scale mass spectrometry imaging data in chemically augmented histology. Sci Rep. 2018 03 06;8(1):4053 Authors: Veselkov K, Sleeman J, Claude E, Vissers JPC, Galea D, Mroz A, Laponogov I, Towers M, Tonge R, Mirnezami R, Takats Z, Nicholson JK, Langridge JI Abstract Mass Spectrometry Imaging (MSI) holds significant promise in augmenting digital histopathologic analysis by generating highly robust big data about the metabolic, lipidomic and proteomic molecular content of the samples. In the process, a vast quantity of unrefined data, that can amount to several hundred gigabytes per tissue section, is produced. Managing, analysing and interpreting this data is a significant challenge and represents a major barrier to the translational application of MSI. Existing data analysis solutions for MSI rely on a set of heterogeneous bioinformatics packages that are not scalable for the reproducible processing of large-scale (hundreds to thousands) biological sample sets. Here, we present a computational platform (pyBASIS) capable of optimized and scalable processing of MSI data for improved information recovery and comparative analysis across tissue specimens using machine learning and related pattern recognition approaches. The proposed solution also provides a means of seamlessly integrating experimental laboratory data with downstream bioinformatics interpretation/analyses, resulting in a truly integrated system for translational MSI. PMID: 29511258 [PubMed - indexed for MEDLINE]

Rice intermediate filament, OsIF, stabilizes photosynthetic machinery and yield under salinity and heat stress.

Sat, 21/09/2019 - 12:21
Related Articles Rice intermediate filament, OsIF, stabilizes photosynthetic machinery and yield under salinity and heat stress. Sci Rep. 2018 03 06;8(1):4072 Authors: Soda N, Gupta BK, Anwar K, Sharan A, Govindjee, Singla-Pareek SL, Pareek A Abstract Cytoskeleton plays a vital role in stress tolerance; however, involvement of intermediate filaments (IFs) in such a response remains elusive in crop plants. This study provides clear evidence about the unique involvement of IFs in cellular protection against abiotic stress in rice. Transcript abundance of Oryza sativa intermediate filament (OsIF) encoding gene showed 2-10 fold up-regulation under different abiotic stress. Overexpression of OsIF in transgenic rice enhanced tolerance to salinity and heat stress, while its knock-down (KD) rendered plants more sensitive thereby indicating the role of IFs in promoting survival under stress. Seeds of OsIF overexpression rice germinated normally in the presence of high salt, showed better growth, maintained chloroplast ultrastructure and favourable K+/Na+ ratio than the wild type (WT) and KD plants. Analysis of photosynthesis and chlorophyll a fluorescence data suggested better performance of both photosystem I and II in the OsIF overexpression rice under salinity stress as compared to the WT and KD. Under salinity and high temperature stress, OsIF overexpressing plants could maintain significantly high yield, while the WT and KD plants could not. Further, metabolite profiling revealed a 2-4 fold higher accumulation of proline and trehalose in OsIF overexpressing rice than WT, under salinity stress. PMID: 29511223 [PubMed - indexed for MEDLINE]

metabolomics; +32 new citations

Fri, 20/09/2019 - 15:11
32 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 2019/09/20PubMed 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; +32 new citations

Fri, 20/09/2019 - 12:10
32 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 2019/09/20PubMed 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; +33 new citations

Thu, 19/09/2019 - 15:01
33 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 2019/09/19PubMed 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, 17/09/2019 - 17:34
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 2019/09/17PubMed 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, 17/09/2019 - 14:33
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 2019/09/17PubMed 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.

Toward collaborative open data science in metabolomics using Jupyter Notebooks and cloud computing.

Mon, 16/09/2019 - 14:24
Related Articles Toward collaborative open data science in metabolomics using Jupyter Notebooks and cloud computing. Metabolomics. 2019 Sep 14;15(10):125 Authors: Mendez KM, Pritchard L, Reinke SN, Broadhurst DI Abstract BACKGROUND: A lack of transparency and reporting standards in the scientific community has led to increasing and widespread concerns relating to reproduction and integrity of results. As an omics science, which generates vast amounts of data and relies heavily on data science for deriving biological meaning, metabolomics is highly vulnerable to irreproducibility. The metabolomics community has made substantial efforts to align with FAIR data standards by promoting open data formats, data repositories, online spectral libraries, and metabolite databases. Open data analysis platforms also exist; however, they tend to be inflexible and rely on the user to adequately report their methods and results. To enable FAIR data science in metabolomics, methods and results need to be transparently disseminated in a manner that is rapid, reusable, and fully integrated with the published work. To ensure broad use within the community such a framework also needs to be inclusive and intuitive for both computational novices and experts alike. AIM OF REVIEW: To encourage metabolomics researchers from all backgrounds to take control of their own data science, mould it to their personal requirements, and enthusiastically share resources through open science. KEY SCIENTIFIC CONCEPTS OF REVIEW: This tutorial introduces the concept of interactive web-based computational laboratory notebooks. The reader is guided through a set of experiential tutorials specifically targeted at metabolomics researchers, based around the Jupyter Notebook web application, GitHub data repository, and Binder cloud computing platform. PMID: 31522294 [PubMed - in process]

An Integrated Gaussian Graphical Model to evaluate the impact of exposures on metabolic networks.

Mon, 16/09/2019 - 14:24
Related Articles An Integrated Gaussian Graphical Model to evaluate the impact of exposures on metabolic networks. Comput Biol Med. 2019 Aug 31;114:103417 Authors: Lee JW, Moen EL, Punshon T, Hoen AG, Stewart D, Li H, Karagas MR, Gui J Abstract Examining the effects of exogenous exposures on complex metabolic processes poses the unique challenge of identifying interactions among a large number of metabolites. Recent progress in the quantification of the metabolome through mass spectrometry (MS) and nuclear magnetic resonance (NMR) has given rise to high-dimensional biomedical data of specific metabolites that can be leveraged to study their effects in humans. These metabolic interactions can be evaluated using probabilistic graphical models (PGMs), which define conditional dependence and independence between components within and between heterogeneous biomedical datasets. This method allows for the detection and recovery of valuable but latent information that cannot be easily detected by other currently existing methods. Here, we develop a PGM method, referred to as an "Integrated Gaussian Graphical Model (IGGM)", to incorporate exposure concentrations of seven trace elements-arsenic (As), lead (Pb), mercury (Hg), cadmium (Cd), zinc (Zn), selenium (Se) and copper (Cu-into metabolic networks. We first conducted a simulation study demonstrating that the integration of trace elements into metabolomics data can improve the accuracy of detecting latent interactions of metabolites impacted by exposure in the network. We tested parameters such as sample size and the number of neighboring metabolites of a chosen trace element for their impact on the accuracy of detecting metabolite interactions. We then applied this method to measurements of cord blood plasma metabolites and placental trace elements collected from newborns in the New Hampshire Birth Cohort Study (NHBCS). We found that our approach can identify latent interactions among metabolites that are related to trace element concentrations. Application to similarly structured data may contribute to our understanding of the complex interplay between exposure-related metabolic interactions that are important for human health. PMID: 31521894 [PubMed - as supplied by publisher]

Metabolomics and transcriptomics reveal defense mechanism of rice (Oryza sativa) grains under stress of 2,2',4,4'-tetrabromodiphenyl ether.

Mon, 16/09/2019 - 14:24
Related Articles Metabolomics and transcriptomics reveal defense mechanism of rice (Oryza sativa) grains under stress of 2,2',4,4'-tetrabromodiphenyl ether. Environ Int. 2019 Sep 12;133(Pt A):105154 Authors: Chen J, Le XC, Zhu L Abstract 2,2',4,4'-Tetrabromodiphenyl ether (BDE-47), a predominant polybrominated diphenyl ether (PBDE), has received extensive attention for its potential environmental impact. An integrated study of metabolomics and transcriptomics was conducted on two rice (Oryza sativa) cultivars, Lianjing-7 (LJ-7) and Yongyou-9 (YY-9), which have been identified as tolerant and sensitive cultivars to BDE-47, respectively. The objective was to investigate the molecular mechanisms of their different ability to tolerate BDE-47. Both rice plants were cultivated to maturity in soils containing three concentrations of BDE-47 (10, 20, and 50 mg/kg). Metabolomic analyses of rice grains identified 65 metabolites in LJ-7 and 45 metabolites in YY-9, including amino acids, saccharides, organic acids, fatty acids, and secondary metabolites. In the tolerant cultivar LJ-7 exposed to 50 mg/kg BDE-47, concentrations of most of the metabolites increased significantly, with α-ketoglutaric acid increased by 20-fold and stigmastanol increased by 12-fold. In the sensitive cultivar YY-9, the concentrations of most metabolites increased after the plant was exposed to 1 and 10 mg/kg BDE-47 but decreased after the plant was exposed to 50 mg/kg BDE-47. Transcriptomic data demonstrated that regulation of gene expressions was affected most in LJ-7 exposed to 50 mg/kg BDE-47 (966 genes up-regulated and 620 genes down-regulated) and in YY-9 exposed to 10 mg/kg BDE-47 (85 genes up-regulated and 291 genes down-regulated), in good accordance with the observed metabolic alternation in the two cultivars. Analyses of metabolic pathways and KEGG enrichment revealed that many biological processes, including energy consumption and biosynthesis, were perturbed in the two rice cultivars by BDE-47. A majority of metabolites and genes involved in dominating pathways of energy consumption (e.g., tricarboxylic acid cycle) and the biosynthesis (e.g., metabolism of saccharides and amino acids) were enhanced in LJ-7 by BDE-47. In contrast, energy consumption was increased while biosynthetic processes were inhibited in YY-9 by BDE-47, which could lead to the sensitivity of YY-9 to BDE-47. The combined results suggest that the different defensive abilities of these two rice cultivars in response to BDE-47 could be attributed to their differences in energy-consumption strategy and biosynthesis of nutritional components in grains. This study provides a useful reference for rice cultivation in PBDE-polluted areas. PMID: 31521816 [PubMed - as supplied by publisher]

Skin metabolome reveals immune responses in yellow drum Nibea albiflora to Cryptocaryon irritans infection.

Mon, 16/09/2019 - 14:24
Related Articles Skin metabolome reveals immune responses in yellow drum Nibea albiflora to Cryptocaryon irritans infection. Fish Shellfish Immunol. 2019 Sep 12;: Authors: Maha IF, Xie X, Zhou S, Yu Y, Liu X, Zahid A, Lei Y, Ma R, Yin F, Qian D Abstract The yellow drum Nibea albiflora is less susceptible to Cryptocaryon irritans infection than is the case with other marine fishes such as Larimichthys crocea, Lateolabrax japonicus, and Pagrus major. To investigate further their resistance mechanism, we infected the N. albiflora with the C. irritans at a median lethal concentration of 2050 theronts/g fish. The skins of the infected and the uninfected fishes were sampled at 24 h and 72 h followed by an extensive analysis of metabolism. The study results revealed that there were 2694 potential metabolites. At 24 h post-infection, 12 metabolites were up-regulated and 17 were down-regulated whereas at 72 h post-infection, 22 metabolites were up-regulated and 26 were down-regulated. Pathway enrichment analysis shows that the differential enriched pathways were higher at 24 h with 22 categories and 58 subcategories (49 up, 9 down) than at 72 h whereby the differential enriched pathways were 6 categories and 8 subcategories (4 up, 4 down). In addition, the principal component analysis (PCA) plot shows that at 24 h the metabolites composition of infected group were separately clustered to uninfected group while at 72 h the metabolites composition in infected group were much closer to uninfected group. This indicated that C. irritans caused strong metabolic stress on the N. albiflora at 24 h and restoration of the dysregulated metabolic state took place at 72 h of infection. Also, at 72 h post infection a total of 17 compounds were identified as potential biomarkers. Furthermore, out of 2694 primary metabolites detected, 23 metabolites could be clearly identified and semi quantified with a known identification number and assigned into 66 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. Most of the enriched KEGG pathways were mainly from metabolic pathway classes, including the metabolic pathway, biosynthesis of secondary metabolites, taurine and hypotaurine metabolism, purine metabolism, linoleic acid metabolism, phenylalanine, tyrosine and tryptophan biosynthesis. Others were glyoxylate and dicarboxylate metabolism, glutathione metabolism, and alanine, aspartate, and glutamate metabolism. Moreover, out of the identified metabolites, only 6 metabolites were statistically differentially expressed, namely, L -glutamate (up-regulated) at 24 h was important for energy and precursor for other glutathiones and instruments of preventing oxidative injury; 15-hydroxy- eicosatetraenoic acid (15-HETE), (S)-(-)-2-Hydroxyisocaproic acid, and adenine (up-regulated) at 72 h were important for anti-inflammatory and immune responses during infection; others were delta-valerolactam and betaine which were down-regulated compared to uninfected group at 72 h, might be related to immure responses including stimulation of immune system such as production of antibodies. Our results therefore further advance our understanding on the immunological regulation of N. albiflora during immune response against infections as they indicated a strong relationship between skin metabolome and C. irritans infection. PMID: 31521785 [PubMed - as supplied by publisher]

Commensal-derived metabolites govern Vibrio cholerae pathogenesis in host intestine.

Mon, 16/09/2019 - 14:24
Related Articles Commensal-derived metabolites govern Vibrio cholerae pathogenesis in host intestine. Microbiome. 2019 Sep 14;7(1):132 Authors: You JS, Yong JH, Kim GH, Moon S, Nam KT, Ryu JH, Yoon MY, Yoon SS Abstract BACKGROUND: Recent evidence suggests that the commensal microbes act as a barrier against invading pathogens and enteric infections are the consequences of multi-layered interactions among commensals, pathogens, and the host intestinal tissue. However, it remains unclear how perturbations of the gut microbiota compromise host infection resistance, especially through changes at species and metabolite levels. RESULTS: Here, we illustrate how Bacteroides vulgatus, a dominant species of the Bacteroidetes phylum in mouse intestine, suppresses infection by Vibrio cholerae, an important human pathogen. Clindamycin (CL) is an antibiotic that selectively kills anaerobic bacteria, and accordingly Bacteroidetes are completely eradicated from CL-treated mouse intestines. The Bacteroidetes-depleted adult mice developed severe cholera-like symptoms, when infected with V. cholerae. Germ-free mice mono-associated with B. vulgatus became resistant to V. cholerae infection. Levels of V. cholerae growth-inhibitory metabolites including short-chain fatty acids plummeted upon CL treatment, while levels of compounds that enhance V. cholerae proliferation were elevated. Furthermore, the intestinal colonization process of V. cholerae was well-simulated in CL-treated adult mice. CONCLUSIONS: Overall, we provide insights into how a symbiotic microbe and a pathogenic intruder interact inside host intestine. We identified B. vulgatus as an indigenous microbial species that can suppress intestinal infection. Our results also demonstrate that commensal-derived metabolites are a critical determinant for host resistance against V. cholerae infection, and that CL pretreatment of adult mice generates a simple yet useful model of cholera infection. PMID: 31521198 [PubMed - in process]

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