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: 2 hours 50 min ago

Integrated analysis of genomics, longitudinal metabolomics, and Alzheimer's risk factors among 1,111 cohort participants.

Mon, 20/05/2019 - 14:03
Related Articles Integrated analysis of genomics, longitudinal metabolomics, and Alzheimer's risk factors among 1,111 cohort participants. Genet Epidemiol. 2019 May 18;: Authors: Darst BF, Lu Q, Johnson SC, Engelman CD Abstract Although Alzheimer's disease (AD) is highly heritable, genetic variants are known to be associated with AD only explain a small proportion of its heritability. Genetic factors may only convey disease risk in individuals with certain environmental exposures, suggesting that a multiomics approach could reveal underlying mechanisms contributing to complex traits, such as AD. We developed an integrated network to investigate relationships between metabolomics, genomics, and AD risk factors using Wisconsin Registry for Alzheimer's Prevention participants. Analyses included 1,111 non-Hispanic Caucasian participants with whole blood expression for 11,376 genes (imputed from dense genome-wide genotyping), 1,097 fasting plasma metabolites, and 17 AD risk factors. A subset of 155 individuals also had 364 fastings cerebral spinal fluid (CSF) metabolites. After adjusting each of these 12,854 variables for potential confounders, we developed an undirected graphical network, representing all significant pairwise correlations upon adjusting for multiple testing. There were many instances of genes being indirectly linked to AD risk factors through metabolites, suggesting that genes may influence AD risk through particular metabolites. Follow-up analyses suggested that glycine mediates the relationship between carbamoyl-phosphate synthase 1 and measures of cardiovascular and diabetes risk, including body mass index, waist-hip ratio, inflammation, and insulin resistance. Further, 38 CSF metabolites explained more than 60% of the variance of CSF levels of tau, a detrimental protein that accumulates in the brain of AD patients and is necessary for its diagnosis. These results further our understanding of underlying mechanisms contributing to AD risk while demonstrating the utility of generating and integrating multiple omics data types. PMID: 31104335 [PubMed - as supplied by publisher]

Correction to: Assessing the effect of nitisinone induced hypertyrosinaemia on monoamine neurotransmitters in brain tissue from a murine model of alkaptonuria using mass spectrometry imaging.

Mon, 20/05/2019 - 14:03
Related Articles Correction to: Assessing the effect of nitisinone induced hypertyrosinaemia on monoamine neurotransmitters in brain tissue from a murine model of alkaptonuria using mass spectrometry imaging. Metabolomics. 2019 May 18;15(5):81 Authors: Davison AS, Strittmatter N, Sutherland H, Hughes AT, Hughes J, Bou-Gharios G, Milan AM, Goodwin RJA, Ranganath LR, Gallagher JA Abstract The original publication of this article contained an incorrect version that did not include some final reviewers' suggestions, was inadvertently received for production and published. The original article has been corrected. PMID: 31104147 [PubMed - in process]

Integrated Regulation of HuR by Translation Repression and Protein Degradation Determines Pulsatile Expression of p53 Under DNA Damage.

Mon, 20/05/2019 - 14:03
Related Articles Integrated Regulation of HuR by Translation Repression and Protein Degradation Determines Pulsatile Expression of p53 Under DNA Damage. iScience. 2019 May 04;15:342-359 Authors: Guha A, Ahuja D, Das Mandal S, Parasar B, Deyasi K, Roy D, Sharma V, Willard B, Ghosh A, Ray PS Abstract Expression of tumor suppressor p53 is regulated at multiple levels, disruption of which often leads to cancer. We have adopted an approach combining computational systems modeling with experimental validation to elucidate the translation regulatory network that controls p53 expression post DNA damage. The RNA-binding protein HuR activates p53 mRNA translation in response to UVC-induced DNA damage in breast carcinoma cells. p53 and HuR levels show pulsatile change post UV irradiation. The computed model fitted with the observed pulse of p53 and HuR only when hypothetical regulators of synthesis and degradation of HuR were incorporated. miR-125b, a UV-responsive microRNA, was found to represses the translation of HuR mRNA. Furthermore, UV irradiation triggered proteasomal degradation of HuR mediated by an E3-ubiquitin ligase tripartite motif-containing 21 (TRIM21). The integrated action of miR-125b and TRIM21 constitutes an intricate control system that regulates pulsatile expression of HuR and p53 and determines cell viability in response to DNA damage. PMID: 31103853 [PubMed - as supplied by publisher]

Integrative transcriptomics, proteomics, and metabolomics data analysis exploring the injury mechanism of ricin on human lung epithelial cells.

Mon, 20/05/2019 - 14:03
Related Articles Integrative transcriptomics, proteomics, and metabolomics data analysis exploring the injury mechanism of ricin on human lung epithelial cells. Toxicol In Vitro. 2019 May 16;: Authors: Xu N, Dong M, Wang Y, Chang Y, Wan J, Zhu W, Wang J, Liu W Abstract Ricin (RT) is a plant toxin belonging to the family of type II ribosome-inactivating protein with high bioterrorism potential. Aerosol RT exposure is the most lethal route, but its mechanism of injury needs further investigation. In the present study, we performed a comprehensive transcriptomics, proteomics and metabolomics analysis on the potential mechanism of injury caused by RT on human lung epithelial cells. In total, 5872 genes, 187 proteins, and 143 metabolites were shown to be significantly changed in human lung epithelial cells after RT treatment. Molecular function, pathway, and network analyses, the genes and proteins regulated in RT-treated cells were mainly attributed to fatty acid metabolism, arginine and proline metabolism and ubiquitin-mediated proteolysis pathway. Furthermore, a comprehensive analysis of transcripts, proteins, and metabolites was performed. The results revealed the correlated genes, proteins, and metabolic pathways regulated in metabolic pathways, amino acid metabolism, transcription and energy metabolism. These genes, proteins, and metabolites involved in these dis-regulated pathways may provide a more targeted and credible direction to study the mechanism of RT injury on human lung epithelial cells. This study provides large-scale omics data that can be used to develop a new strategy for the prevention, rapid diagnosis, and treatment of RT poisoning, especially of RT aerosol. PMID: 31103672 [PubMed - as supplied by publisher]

Metabolomics workflow for lung cancer: Discovery of biomarkers.

Mon, 20/05/2019 - 14:03
Related Articles Metabolomics workflow for lung cancer: Discovery of biomarkers. Clin Chim Acta. 2019 May 16;: Authors: Tang Y, Li Z, Lazar L, Fang Z, Tang C, Zhao J Abstract Lung cancer is one of the most common cancers in the world. Due to the limitations of current diagnostic techniques and methods, most lung cancers are diagnosed at the advanced stage, which is not conducive to early treatment. The rise of metabolomics has provided new ideas for the early diagnosis of lung cancer. As a method for the comprehensive analysis of endogenous metabolites of the biological system, metabolomics has shown significant application potential for the early diagnosis and individualized treatment of various cancers including lung cancers. Via advanced analytical techniques and bioinformatics tools, the metabolome was excavated to find biomarkers related to cancer and its prognosis. In this review, the research methods and workflow of metabolomics are summarized, with an emphasis on the recent discovery of biomarkers and major metabolic pathways for lung cancers. PMID: 31103622 [PubMed - as supplied by publisher]

Targeting bioactive compounds in natural extracts - Development of a comprehensive workflow combining chemical and biological data.

Mon, 20/05/2019 - 14:03
Related Articles Targeting bioactive compounds in natural extracts - Development of a comprehensive workflow combining chemical and biological data. Anal Chim Acta. 2019 Sep 06;1070:29-42 Authors: Ory L, Nazih EH, Daoud S, Mocquard J, Bourjot M, Margueritte L, Delsuc MA, Bard JM, Pouchus YF, Bertrand S, Roullier C Abstract In natural product drug discovery, several strategies have emerged to highlight specifically bioactive compound(s) within complex mixtures (fractions or crude extracts) using metabolomics tools. In this area, a great deal of interest has raised among the scientific community on strategies to link chemical profiles and associated biological data, leading to the new field called "biochemometrics". This article falls into this emerging research by proposing a complete workflow, which was divided into three major steps. The first one consists in the fractionation of the same extract using four different chromatographic stationary phases and appropriated elution conditions to obtain five fractions for each column. The second step corresponds to the acquisition of chemical profiles using HPLC-HRMS analysis, and the biological evaluation of each fraction. The last step evaluates the links between the relative abundances of molecules present in fractions (peak area) and the global bioactivity level observed for each fraction. To this purpose, an original bioinformatics script (encoded with R Studio software) using the combination of four statistical models (Spearman, F-PCA, PLS, PLS-DA) was here developed leading to the generation of a "Super list" of potential bioactive compounds together with a predictive score. This strategy was validated by its application on a marine-derived Penicillium chrysogenum extract exhibiting antiproliferative activity on breast cancer cells (MCF-7 cells). After the three steps of the workflow, one main compound was highlighted as responsible for the bioactivity and identified as ergosterol. Its antiproliferative activity was confirmed with an IC50 of 0.10 μM on MCF-7 cells. The script efficiency was further demonstrated by comparing the results obtained with a different recently described approach based on NMR profiling and by virtually modifying the data to evaluate the computational tool behaviour. This approach represents a new and efficient tool to tackle some of the bottlenecks in natural product drug discovery programs. PMID: 31103165 [PubMed - in process]

Rhizosphere microbiomes diverge among Populus trichocarpa plant-host genotypes and chemotypes, but it depends on soil origin.

Mon, 20/05/2019 - 14:03
Related Articles Rhizosphere microbiomes diverge among Populus trichocarpa plant-host genotypes and chemotypes, but it depends on soil origin. Microbiome. 2019 May 18;7(1):76 Authors: Veach AM, Morris R, Yip DZ, Yang ZK, Engle NL, Cregger MA, Tschaplinski TJ, Schadt CW Abstract BACKGROUND: Plants have developed defense strategies for phytopathogen and herbivore protection via coordinated metabolic mechanisms. Low-molecular weight metabolites produced within plant tissues, such as salicylic acid, represent one such mechanism which likely mediates plant - microbe interactions above and below ground. Salicylic acid is a ubiquitous phytohormone at low levels in most plants, yet are concentrated defense compounds in Populus, likely acting as a selective filter for rhizosphere microbiomes. We propagated twelve Populus trichocarpa genotypes which varied an order of magnitude in salicylic acid (SA)-related secondary metabolites, in contrasting soils from two different origins. After four months of growth, plant properties (leaf growth, chlorophyll content, and net photosynthetic rate) and plant root metabolomics specifically targeting SA metabolites were measured via GC-MS. In addition, rhizosphere microbiome composition was measured via Illumina MiSeq sequencing of 16S and ITS2 rRNA-genes. RESULTS: Soil origin was the primary filter causing divergence in bacterial/archaeal and fungal communities with plant genotype secondarily influential. Both bacterial/archaeal and fungal evenness varied between soil origins and bacterial/archaeal diversity and evenness correlated with at least one SA metabolite (diversity: populin; evenness: total phenolics). The production of individual salicylic acid derivatives that varied by host genotype resulted in compositional differences for bacteria /archaea (tremuloidin) and fungi (salicylic acid) within one soil origin (Clatskanie) whereas soils from Corvallis did not illicit microbial compositional changes due to salicylic acid derivatives. Several dominant bacterial (e.g., Betaproteobacteria, Acidobacteria, Verrucomicrobia, Chloroflexi, Gemmatimonadete, Firmicutes) and one fungal phyla (Mortierellomycota) also correlated with specific SA secondary metabolites; bacterial phyla exhibited more negative interactions (declining abundance with increasing metabolite concentration) than positive interactions. CONCLUSIONS: These results indicate microbial communities diverge most among soil origin. However, within a soil origin, bacterial/archaeal communities are responsive to plant SA production within greenhouse-based rhizosphere microbiomes. Fungal microbiomes are impacted by root SA-metabolites, but overall to a lesser degree within this experimental context. These results suggest plant defense strategies, such as SA and its secondary metabolites, may partially drive patterns of both bacterial/archaeal and fungal taxa-specific colonization and assembly. PMID: 31103040 [PubMed - in process]

High temperature-induced proteomic and metabolomic profiles of a thermophilic Bacillus manusensis isolated from the deep-sea hydrothermal field of Manus Basin.

Sun, 19/05/2019 - 13:35
Related Articles High temperature-induced proteomic and metabolomic profiles of a thermophilic Bacillus manusensis isolated from the deep-sea hydrothermal field of Manus Basin. J Proteomics. 2019 May 15;:103380 Authors: Sun QL, Sun YY, Zhang J, Luan ZD, Lian C, Liu SQ, Yu C Abstract Thermophiles are organisms that grow optimally at 50 °C-80 °C and studies on the survival mechanisms of thermophiles have drawn great attention. Bacillus manusensis S50-6 is the type strain of a new thermophilic species isolated from hydrothermal vent in Manus Basin. In this study, we examined the growth and global responses of S50-6 to high temperature on molecular level using multi-omics method (genomics, proteomics, and metabolomics). S50-6 grew optimally at 50 °C (Favorable, F) and poorly at 65 °C (Non-Favorable, NF); it formed spores at F but not at NF condition. At NF condition, S50-6 formed long filaments containing undivided cells. A total of 1621 proteins were identified at F and NF conditions, and 613 proteins were differentially expressed between F and NF. At NF condition, proteins of glycolysis, rRNA mature and modification, and DNA/protein repair were up-regulated, whereas proteins of sporulation and amino acid/nucleotide metabolism were down-regulated. Consistently, many metabolites associated with amino acid and nucleotide metabolic processes were down-regulated at NF condition. Our results revealed molecular strategies of deep-sea B. manusensis to survive at unfavorable high temperature and provided new insights into the thermotolerant mechanisms of thermophiles. SIGNIFICANCE: In this study, we systematically characterized the genomic, proteomic and metabolomic profiles of a thermophilic deep-sea Bacillus manusensis under different temperatures. Based on these analysis, we propose a model delineating the global responses of B. manusensis to unfavorable high temperature. Under unfavorable high temperature, glycolysis is a more important energy supply pathway; protein synthesis is subjected to more stringent regulation by increased tRNA modification; protein and DNA repair associated proteins are enhanced in production to promote heat survival. In contrast, energy-costing pathways, such as sporulation, are repressed, and basic metabolic pathways, such as amino acid and nucleotide metabolisms, are slowed down. Our results provide new insights into the thermotolerant mechanisms of thermophilic Bacillus. PMID: 31102757 [PubMed - as supplied by publisher]

Metabolome Wide Association Study of serum DDT and DDE in Pregnancy and Early Postpartum.

Sun, 19/05/2019 - 13:35
Related Articles Metabolome Wide Association Study of serum DDT and DDE in Pregnancy and Early Postpartum. Reprod Toxicol. 2019 May 15;: Authors: Hu X, Li S, Cirrilo P, Krigbaum N, Tran V, Ishikawa T, La Merrill MA, Jones DP, Cohn B Abstract The advancement of high-resolution metabolomics (HRM) and metabolome-wide-association study (MWAS) enables the readout of environmental effects in human specimens. We used HRM to understand DDT-induced alterations of in utero environment and potential health effects. Endogenous metabolites were measured in 397 maternal perinatal serum samples collected during 1959-1967 in the Child Health and Development Studies (CHDS) and in 16 maternal postnatal serum samples of mice treated with or without DDT. MWAS was performed to assess associations between metabolites and p,p'-DDT, o,p'-DDT and p,p'-DDE levels, followed by pathway analysis. Distinct metabolic profiles were found with p,p'-DDT and p,p'-DDE. Amino acids such arginine had a strong association with p,p'-DDT and o,p'-DDT in both women and mice, whereas lipids and acyl-carnitine intermediates were found exclusively associated with p,p'-DDE in CHDS women indicating mitochondrial impairment. It suggests that the role of serine and fatty acid metabolism on the causal disease pathway should be examined. PMID: 31102720 [PubMed - as supplied by publisher]

Capturing the complex interplay between drugs and the intestinal microbiome.

Sun, 19/05/2019 - 13:35
Related Articles Capturing the complex interplay between drugs and the intestinal microbiome. Clin Pharmacol Ther. 2019 May 18;: Authors: Birer C, Wright ES Abstract Predicting drug interactions, disposition, and side effects is central to the practice of clinical pharmacology. Until recently, the human microbiome has been an underappreciated player in the dynamics of drug metabolism. It is now clear that humans are 'superorganisms' with about tenfold more microbial cells than human cells and harboring an immense diversity of microbial enzymes. Owing to the advent of new technologies, we are beginning to understand the human microbiome's impact on clinical pharmacology. This article is protected by copyright. All rights reserved. PMID: 31102465 [PubMed - as supplied by publisher]

Serum metabolic signatures of coronary and carotid atherosclerosis and subsequent cardiovascular disease.

Sun, 19/05/2019 - 13:35
Related Articles Serum metabolic signatures of coronary and carotid atherosclerosis and subsequent cardiovascular disease. Eur Heart J. 2019 May 18;: Authors: Tzoulaki I, Castagné R, Boulangé CL, Karaman I, Chekmeneva E, Evangelou E, Ebbels TMD, Kaluarachchi MR, Chadeau-Hyam M, Mosen D, Dehghan A, Moayyeri A, Ferreira DLS, Guo X, Rotter JI, Taylor KD, Kavousi M, de Vries PS, Lehne B, Loh M, Hofman A, Nicholson JK, Chambers J, Gieger C, Holmes E, Tracy R, Kooner J, Greenland P, Franco OH, Herrington D, Lindon JC, Elliott P Abstract AIMS: To characterize serum metabolic signatures associated with atherosclerosis in the coronary or carotid arteries and subsequently their association with incident cardiovascular disease (CVD). METHODS AND RESULTS: We used untargeted one-dimensional (1D) serum metabolic profiling by proton nuclear magnetic resonance spectroscopy (1H NMR) among 3867 participants from the Multi-Ethnic Study of Atherosclerosis (MESA), with replication among 3569 participants from the Rotterdam and LOLIPOP studies. Atherosclerosis was assessed by coronary artery calcium (CAC) and carotid intima-media thickness (IMT). We used multivariable linear regression to evaluate associations between NMR features and atherosclerosis accounting for multiplicity of comparisons. We then examined associations between metabolites associated with atherosclerosis and incident CVD available in MESA and Rotterdam and explored molecular networks through bioinformatics analyses. Overall, 30 1H NMR measured metabolites were associated with CAC and/or IMT, P = 1.3 × 10-14 to 1.0 × 10-6 (discovery) and P = 5.6 × 10-10 to 1.1 × 10-2 (replication). These associations were substantially attenuated after adjustment for conventional cardiovascular risk factors. Metabolites associated with atherosclerosis revealed disturbances in lipid and carbohydrate metabolism, branched chain, and aromatic amino acid metabolism, as well as oxidative stress and inflammatory pathways. Analyses of incident CVD events showed inverse associations with creatine, creatinine, and phenylalanine, and direct associations with mannose, acetaminophen-glucuronide, and lactate as well as apolipoprotein B (P < 0.05). CONCLUSION: Metabolites associated with atherosclerosis were largely consistent between the two vascular beds (coronary and carotid arteries) and predominantly tag pathways that overlap with the known cardiovascular risk factors. We present an integrated systems network that highlights a series of inter-connected pathways underlying atherosclerosis. PMID: 31102408 [PubMed - as supplied by publisher]

A comparative analysis of egg provisioning using mass spectrometry during rapid life history evolution in sea urchins.

Sun, 19/05/2019 - 13:35
Related Articles A comparative analysis of egg provisioning using mass spectrometry during rapid life history evolution in sea urchins. Evol Dev. 2019 May 17;: Authors: Davidson PL, Thompson JW, Foster MW, Moseley MA, Byrne M, Wray GA Abstract A dramatic life history switch that has evolved numerous times in marine invertebrates is the transition from planktotrophic (feeding) to lecithotrophic (nonfeeding) larval development-an evolutionary tradeoff with many important developmental and ecological consequences. To attain a more comprehensive understanding of the molecular basis for this switch, we performed untargeted lipidomic and proteomic liquid chromatography-tandem mass spectrometry on eggs and larvae from three sea urchin species: the lecithotroph Heliocidaris erythrogramma, the closely related planktotroph Heliocidaris tuberculata, and the distantly related planktotroph Lytechinus variegatus. We identify numerous molecular-level changes possibly associated with the evolution of lecithotrophy in H. erythrogramma. We find the massive lipid stores of H. erythrogramma eggs are largely composed of low-density, diacylglycerol ether lipids that, contrary to expectations, appear to support postmetamorphic development and survivorship. Rapid premetamorphic development in this species may instead be powered by upregulated carbohydrate metabolism or triacylglycerol metabolism. We also find proteins involved in oxidative stress regulation are upregulated in H. erythrogramma eggs, and apoB-like lipid transfer proteins may be important for echinoid oogenic nutrient provisioning. These results demonstrate how mass spectrometry can enrich our understanding of life history evolution and organismal diversity by identifying specific molecules associated with distinct life history strategies and prompt new hypotheses about how and why these adaptations evolve. PMID: 31102332 [PubMed - as supplied by publisher]

Alternative outlets for sustaining photosynthetic electron transport during dark-to-light transitions.

Sun, 19/05/2019 - 13:35
Related Articles Alternative outlets for sustaining photosynthetic electron transport during dark-to-light transitions. Proc Natl Acad Sci U S A. 2019 May 17;: Authors: Saroussi S, Karns DAJ, Thomas DC, Bloszies C, Fiehn O, Posewitz MC, Grossman AR Abstract Environmental stresses dramatically impact the balance between the production of photosynthetically derived energetic electrons and Calvin-Benson-Bassham cycle (CBBC) activity; an imbalance promotes accumulation of reactive oxygen species and causes cell damage. Hence, photosynthetic organisms have developed several strategies to route electrons toward alternative outlets that allow for storage or harmless dissipation of their energy. In this work, we explore the activities of three essential outlets associated with Chlamydomonas reinhardtii photosynthetic electron transport: (i) reduction of O2 to H2O through flavodiiron proteins (FLVs) and (ii) plastid terminal oxidases (PTOX) and (iii) the synthesis of starch. Real-time measurements of O2 exchange have demonstrated that FLVs immediately engage during dark-to-light transitions, allowing electron transport when the CBBC is not fully activated. Under these conditions, we quantified maximal FLV activity and its overall capacity to direct photosynthetic electrons toward O2 reduction. However, when starch synthesis is compromised, a greater proportion of the electrons is directed toward O2 reduction through both the FLVs and PTOX, suggesting an important role for starch synthesis in priming/regulating CBBC and electron transport. Moreover, partitioning energized electrons between sustainable (starch; energetic electrons are recaptured) and nonsustainable (H2O; energetic electrons are not recaptured) outlets is part of the energy management strategy of photosynthetic organisms that allows them to cope with the fluctuating conditions encountered in nature. Finally, unmasking the repertoire and control of such energetic reactions offers new directions for rational redesign and optimization of photosynthesis to satisfy global demands for food and other resources. PMID: 31101712 [PubMed - as supplied by publisher]

ROIMCR: a powerful analysis strategy for LC-MS metabolomic datasets.

Sun, 19/05/2019 - 13:35
Related Articles ROIMCR: a powerful analysis strategy for LC-MS metabolomic datasets. BMC Bioinformatics. 2019 May 17;20(1):256 Authors: Gorrochategui E, Jaumot J, Tauler R Abstract BACKGROUND: The analysis of LC-MS metabolomic datasets appears to be a challenging task in a wide range of disciplines since it demands the highly extensive processing of a vast amount of data. Different LC-MS data analysis packages have been developed in the last few years to facilitate this analysis. However, most of these strategies involve chromatographic alignment and peak shaping and often associate each "feature" (i.e., chromatographic peak) with a unique m/z measurement. Thus, the development of an alternative data analysis strategy that is applicable to most types of MS datasets and properly addresses these issues is still a challenge in the metabolomics field. RESULTS: Here, we present an alternative approach called ROIMCR to: i) filter and compress massive LC-MS datasets while transforming their original structure into a data matrix of features without losing relevant information through the search of regions of interest (ROIs) in the m/z domain and ii) resolve compressed data to identify their contributing pure components without previous alignment or peak shaping by applying a Multivariate Curve Resolution-Alternating Least Squares (MCR-ALS) analysis. In this study, the basics of the ROIMCR method are presented in detail and a detailed description of its implementation is also provided. Data were analyzed using the MATLAB (The MathWorks, Inc., www.mathworks.com ) programming and computing environment. The application of the ROIMCR methodology is described in detail, with an example of LC-MS data generated in a lipidomic study and with other examples of recent applications. CONCLUSIONS: The methodology presented here combines the benefits of data filtering and compression based on the searching of ROI features, without the loss of spectral accuracy. The method has the benefits of the application of the powerful MCR-ALS data resolution method without the necessity of performing chromatographic peak alignment or modelling. The presented method is a powerful alternative to other existing data analysis approaches that do not use the MCR-ALS method to resolve LC-MS data. The ROIMCR method also represents an improved strategy compared to the direct applications of the MCR-ALS method that use less-powerful data compression strategies such as binning and windowing. Overall, the strategy presented here confirms the usefulness of the ROIMCR chemometrics method for analyzing LC-MS untargeted metabolomics data. PMID: 31101001 [PubMed - in process]

Integrative Metabolomic and Transcriptomic Analysis for the Study of Bladder Cancer.

Sun, 19/05/2019 - 13:35
Related Articles Integrative Metabolomic and Transcriptomic Analysis for the Study of Bladder Cancer. Cancers (Basel). 2019 May 16;11(5): Authors: Loras A, Suárez-Cabrera C, Martínez-Bisbal MC, Quintás G, Paramio JM, Martínez-Máñez R, Gil S, Ruiz-Cerdá JL Abstract Metabolism reprogramming is considered a hallmark of cancer. The study of bladder cancer (BC) metabolism could be the key to developing new strategies for diagnosis and therapy. This work aimed to identify tissue and urinary metabolic signatures as biomarkers of BC and get further insight into BC tumor biology through the study of gene-metabolite networks and the integration of metabolomics and transcriptomics data. BC and control tissue samples (n = 44) from the same patients were analyzed by High-Resolution Magic Angle Spinning Nuclear Magnetic Resonance and microarrays techniques. Besides, urinary profiling study (n = 35) was performed in the same patients to identify a metabolomic profile, linked with BC tissue hallmarks, as a potential non-invasive approach for BC diagnosis. The metabolic profile allowed for the classification of BC tissue samples with a sensitivity and specificity of 100%. The most discriminant metabolites for BC tissue samples reflected alterations in amino acids, glutathione, and taurine metabolic pathways. Transcriptomic data supported metabolomic results and revealed a predominant downregulation of metabolic genes belonging to phosphorylative oxidation, tricarboxylic acid cycle, and amino acid metabolism. The urinary profiling study showed a relation with taurine and other amino acids perturbed pathways observed in BC tissue samples, and classified BC from non-tumor urine samples with good sensitivities (91%) and specificities (77%). This urinary profile could be used as a non-invasive tool for BC diagnosis and follow-up. PMID: 31100982 [PubMed]

Dose-Dependent Sorafenib-Induced Immunosuppression Is Associated with Aberrant NFAT Activation and Expression of PD-1 in T Cells.

Sun, 19/05/2019 - 13:35
Related Articles Dose-Dependent Sorafenib-Induced Immunosuppression Is Associated with Aberrant NFAT Activation and Expression of PD-1 in T Cells. Cancers (Basel). 2019 May 16;11(5): Authors: Iyer RV, Maguire O, Kim M, Curtin LI, Sexton S, Fisher DT, Schihl SA, Fetterly G, Menne S, Minderman H Abstract The multikinase inhibitor sorafenib is the only standard first-line therapy for hepatocellular carcinoma (HCC). Here, we report the dose-dependent effects of sorafenib on the immune response, which is related to nuclear factor of activated T cells 1 (NFAT1) activity. In vitro and in vivo experiments were performed with low and high doses of sorafenib using human T cells and spontaneous developed woodchuck HCC models. In vitro studies demonstrated that following exposure to a high dose of sorafenib the baseline activity of NFAT1 in T cells was significantly increased. In a parallel event, high dose sorafenib resulted in a significant decrease in T cell proliferation and increased the proportion of PD-1 expressing CD8+ T cells with NFAT1 activation. In the in vivo model, smaller tumors were detected in the low-dose sorafenib treated group compared to the placebo and high-dose treated groups. The low-dose sorafenib group showed a significant tumor growth delay with significantly more CD3+ cells in tumor. This study demonstrates that sorafenib has immunomodulatory effects in a dose- and time-dependent manner. Higher dose of sorafenib treatment was associated with immunosuppressive action. This observed effect of sorafenib should be taken into consideration in the selection of optimum starting dose for future trials. PMID: 31100868 [PubMed]

metabolomics; +22 new citations

Sat, 18/05/2019 - 13:12
22 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 2019/05/18PubMed 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; +21 new citations

Fri, 17/05/2019 - 16:01
21 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 2019/05/17PubMed 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; +21 new citations

Fri, 17/05/2019 - 13:01
21 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 2019/05/17PubMed 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; +35 new citations

Thu, 16/05/2019 - 15:47
35 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 2019/05/16PubMed 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.

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