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

metabolomics; +29 new citations

Sat, 11/07/2020 - 12:32
29 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 2020/07/11PubMed 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; +24 new citations

Fri, 10/07/2020 - 15:18
24 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 2020/07/10PubMed 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; +24 new citations

Fri, 10/07/2020 - 12:18
24 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 2020/07/10PubMed 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; +24 new citations

Thu, 09/07/2020 - 15:05
24 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 2020/07/09PubMed 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; +28 new citations

Wed, 08/07/2020 - 14:42
28 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 2020/07/08PubMed 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

Tue, 07/07/2020 - 14:30
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 2020/07/07PubMed 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.

Gut bacteria of the silkworm Bombyx mori facilitate host resistance against the toxic effects of organophosphate insecticides.

Mon, 06/07/2020 - 14:10
Gut bacteria of the silkworm Bombyx mori facilitate host resistance against the toxic effects of organophosphate insecticides. Environ Int. 2020 Jul 02;143:105886 Authors: Chen B, Zhang N, Xie S, Zhang X, He J, Muhammad A, Sun C, Lu X, Shao Y Abstract Organophosphate insecticides that are heavily used in agriculture for pest control have caused growing environmental problems and public health concerns worldwide. Ironically, insecticide resistance develops quickly in major lepidopteran pests, partially via their microbial symbionts. To investigate the possible mechanisms by which the microbiota confers insecticide resistance to Lepidoptera, the model organism silkworm Bombyx mori (Lepidoptera: Bombycidae) was fed different antibiotics to induce gut dysbiosis (microbiota imbalance). Larvae treated with polymyxin showed a significantly lower survival rate when exposed to chlorpyrifos. Through high-throughput sequencing, we found that the abundances of Stenotrophomonas and Enterococcus spp. changed substantially after treatment. To assess the roles played by these two groups of bacteria in chlorpyrifos resistance, a germ-free (GF) silkworm rearing protocol was established to avoid the influence of natural microbiota and antibiotics. Monoassociation of GF silkworms with Stenotrophomonas enhanced host resistance to chlorpyrifos, but not in Enterococcus-fed larvae, consistent with larval detoxification activity. GC-μECD detection of chlorpyrifos residues in feces indicated that neither Stenotrophomonas nor Enterococcus degraded chlorpyrifos directly in the gut. However, gut metabolomics analysis revealed a highly species-specific pattern, with higher levels of essential amino acid produced in the gut of silkworm larvae monoassociated with Stenotrophomonas. This critical nutrient provisioning significantly increased host fitness and thereby allowed larvae to circumvent the deleterious effects of these toxic chemicals more efficiently. Altogether, our study not only suggests a new mechanism for insecticide resistance in notorious lepidopteran pests but also provides a useful template for investigating the interplay between host and gut bacteria in complex environmental systems. PMID: 32623217 [PubMed - as supplied by publisher]

Metabolomics combined with proteomics provides a novel interpretation of the changes in nonvolatile compounds during white tea processing.

Mon, 06/07/2020 - 14:10
Metabolomics combined with proteomics provides a novel interpretation of the changes in nonvolatile compounds during white tea processing. Food Chem. 2020 Jun 24;332:127412 Authors: Chen Q, Shi J, Mu B, Chen Z, Dai W, Lin Z Abstract In this study, metabolomics and proteomics were employed to investigate the change mechanism of nonvolatile compounds during white tea processing. A total of 99 nonvolatile compounds were identified, among which the contents of 13 free amino acids, caffeine, theaflavins, 7 nucleosides and nucleotides, and 5 flavone glycosides increased significantly, while the contents of theanine, catechins, theasinesins, 3 proanthocyanidins, and phenolic acids decreased significantly during the withering period. The results of proteomics indicated that the degradation of proteins accounted for the increase in free amino acid levels; the weakened biosynthesis, in addition to oxidation, also contributed to the decrease in flavonoid levels; the degradation of ribonucleic acids contributed to the increase in nucleoside and nucleotide levels during the withering period. In addition, the drying process was found to slightly promote the formation of white tea taste. Our study provides a novel characterization of white tea taste formation during processing. PMID: 32623128 [PubMed - as supplied by publisher]

NK cells contribute to hepatic CD8+ T cell failure in hepatitis B virus-carrier mice after alcohol consumption.

Mon, 06/07/2020 - 14:10
NK cells contribute to hepatic CD8+ T cell failure in hepatitis B virus-carrier mice after alcohol consumption. Virus Res. 2020 Jul 02;:198085 Authors: Jiang S, Zhu Y, Cheng C, Li Y, Ma T, Peng Z, Li Q, Xu J, Xu L Abstract Despite the fact that both Hepatitis B virus (HBV) infection and excessive alcohol consumption represent health problems worldwide, the mechanism by which alcohol affected the progression of HBV-associated liver disease are not completely understood. Therefore, we studied how alcohol affects the development of HBV infection and the role of T cells and NK cells in the antiviral response. Mononuclear cells (MNCs) derived from HBV-carrier mice and wild type (WT) mice were characterized for phenotype by flow cytometry, HBV antigen and gene expression were detected by Radio Immunoassay (RIA), immunohistochemistry and quantitative real-time (qRT)-PCR. Metabolomics changes were detected in mice liver tissue based on ultra high performance liquid tandem chromatography quadrupole time of flight mass spectrometry (UHPLC-QTOFMS). The mice after ethanol consumption shows higher levels of HBV surface Ag (HBsAg), HBV core antigen (HBcAg) and HBV 3.5 kb RNA expression, and a lower level of CD8+ T cells during HBV persistence, with an increased lymphocyte activation gene-3 (LAG-3) expression on CD8+ T cell. In addition, the energy metabolism was downregulated and the oxidative stress was upregulated in the liver tissue. Furthermore, NK cells depletion results in a lower levels of HBV surface Ag (HBsAg) and HBV 3.5 kb RNA expression, and a higher level of CD8+ T cells with reduced expression of LAG-3. In conclusion, alcohol abuse induces CD8+ T cells failure after acute HBV infection, but depletion of NK cells could retore CD8+ T cell activity. Moreover, downregulation of energy metabolism and upregulation of oxidative stress may also contribute to CD8+ T cell failure. PMID: 32622853 [PubMed - as supplied by publisher]

Comprehensive arginine metabolomics and peripheral vasodilatory capacity in rheumatoid arthritis: A monocentric cross-sectional study.

Mon, 06/07/2020 - 14:10
Comprehensive arginine metabolomics and peripheral vasodilatory capacity in rheumatoid arthritis: A monocentric cross-sectional study. Microvasc Res. 2020 Jul 02;:104038 Authors: Erre GL, Mangoni AA, Passiu G, Bassu S, Castagna F, Carru C, Piga M, Zinellu A, Sotgia S Abstract BACKGROUND: The relationship between plasma arginine metabolites influencing vascular homeostasis and peripheral vasodilatory capacity in rheumatoid arthritis (RA) patients is not known. METHODS: l-arginine (Arg), monomethyl-l-arginine (MMA), l-homoarginine (hArg), asymmetric dimethyl-l-arginine (ADMA), symmetric dimethyl-l-arginine, and l-citrulline (Cit) were measured by liquid chromatography tandem mass spectrometry (LC-MS/MS) in 164 RA patients and 100 age- and sex-matched healthy controls without previous cardiovascular events. Log-transformed reactive hyperemia index (Ln-RHI) evaluated by flow-mediated pulse amplitude tonometry (PAT, EndoPAT2000 device) was assessed as surrogate measure of peripheral vasodilatory capacity in RA patients. Ln-RHI values <0.51 indicated peripheral endothelial dysfunction (ED). The relationship between plasma arginine metabolite concentrations, RA descriptors and peripheral vasodilatory capacity was evaluated by bivariate correlation and regression analyses. RESULTS: Plasma ADMA concentrations were significantly higher, and plasma hArg concentrations significantly lower, in RA patients than in controls (0.53 ± 0.09 vs 0.465 ± 0.07 μmol/L and 1.50 ± 0.60 vs 1.924 ± 0.78 μmol/L, respectively; p < 0.001 for both comparisons). Bivariate correlation analysis demonstrated no significant correlation between arginine metabolites and disease descriptors. In regression analysis in RA patients, higher plasma ADMA concentrations were independently associated with presence of ED [OR(95% CI) = 77.3(1.478-4050.005), p = 0.031] and lower Ln-RHI [B coefficient(95% CI) = -0.57(-1.09 to -0.05), p = 0.032]. CONCLUSIONS: ADMA was significantly, albeit weakly, associated with impaired microcirculatory vasodilatory capacity and peripheral endothelial dysfunction in RA. This suggests an important pathophysiological role of this metabolite in the vascular alterations observed in this patient group. PMID: 32622695 [PubMed - as supplied by publisher]

Integrated metabolomics and lipidomics reveals high accumulation of polyunsaturated lysoglycerophospholipids in human lung fibroblasts exposed to fine particulate matter.

Mon, 06/07/2020 - 14:10
Integrated metabolomics and lipidomics reveals high accumulation of polyunsaturated lysoglycerophospholipids in human lung fibroblasts exposed to fine particulate matter. Ecotoxicol Environ Saf. 2020 Jul 01;202:110896 Authors: Shon JC, Lee SM, Jung JH, Wu Z, Kwon YS, Sim HJ, Seo JS Abstract Exposure to fine particulate matter (PM) comprising toxic compounds arising from air pollution is a major human health concern. It is linked to increased mortality and incidence of various lung diseases. However, the mechanisms underlying the toxic effects of PM on lung fibroblasts have not been fully explored. We used targeted quantitative metabolomics and lipidomics analysis along with cytotoxicity studies to comprehensively characterize the alterations in the metabolite profiles of human lung fibroblasts (HEL 299) upon exposure to PM2.5 and PM10. This exposure at 50 μg/mL for 72 h induced an abnormally high apoptotic response via triggering intracellular reactive oxygen species (ROS) production and mitochondrial dysfunction through an imbalance between pro- and anti-apoptotic signaling pathways. The cytotoxic effects of PM2.5 were more severe than those of PM10. Metabolomics and lipidomics analyses revealed that PM exposure triggered substantial changes in the cellular metabolite profile, which involved reduced mitochondria-related metabolites such as tricarboxylic acid (TCA) cycle intermediates, amino acids, and free fatty acids as well as increased lysoglycerophospholipids (LPLs) containing polyunsaturated fatty acids. The decrease in mitochondria-related metabolites suggested that PM exposure led to reduced TCA cycle capacity and energy production. Apoptotic and inflammatory responses as well as mitochondrial dysfunction were likely to be accelerated because of excessive accumulation of LPLs, contributing to the disruption of membrane rafts and Ca2+ homeostasis and causing increased mitochondrial ROS formation. These results provide valuable insights regarding the toxic effects of PM exposure. Our study also provides a new direction for research on PM exposure-related health disorders using different cell lines. PMID: 32622306 [PubMed - as supplied by publisher]

Dysregulation of steroid hormone receptors in motor neurons and glia associates with disease progression in ALS mice.

Mon, 06/07/2020 - 14:10
Dysregulation of steroid hormone receptors in motor neurons and glia associates with disease progression in ALS mice. Endocrinology. 2020 Jul 05;: Authors: McLeod VM, Chiam MDF, Lau CL, Rupasinghe TW, Boon WC, Turner BJ Abstract Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease targeting motor neurons which shows sexual dimorphism in its incidence, age of onset and progression rate. All steroid hormones, including androgens, estrogens and progestogens, have been implicated in modulating ALS. Increasing evidence suggests that steroid hormones provide neuroprotective and neurotrophic support to motor neurons, either directly or via surrounding glial cell interactions, by activating their respective nuclear hormone receptors and initiating transcriptional regulatory responses. The SOD1G93A transgenic mouse also shows sex-specific differences in age of onset and progression, and remains the most widely used model in ALS research. To provide a more comprehensive understanding of the influences of steroid hormone signalling in ALS, we systemically characterised sex hormone receptor expression at transcript and protein levels, cellular localisation and the impact of disease course in lumbar spinal cords of male and female SOD1G93A mice. We found that spinal motor neurons highly express nuclear AR, ERα, ERβ and PR with variations in glial cell expression. AR showed the most robust sex-specific difference in expression and was downregulated in male SOD1G93A mouse spinal cord, in association with depletion in 5α-reductase type 2 isoform which primarily metabolises testosterone to DHT. ERα was highly enriched in reactive astrocytes of SOD1G93A mice and ERβ was strongly upregulated. The 5α-reductase type 1 isoform was upregulated with disease progression and may influence local spinal cord hormone levels. In conclusion, steroid hormone receptor expression is dynamic and cell-type specific in SOD1G93A mice which may provide targets to modulate progression in ALS. PMID: 32621747 [PubMed - as supplied by publisher]

Bioaccumulation and toxic effects of penconazole in earthworms (Eisenia fetida) following soil exposure.

Mon, 06/07/2020 - 14:10
Related Articles Bioaccumulation and toxic effects of penconazole in earthworms (Eisenia fetida) following soil exposure. Environ Sci Pollut Res Int. 2020 Jul 03;: Authors: Li R, Meng Z, Sun W, Wu R, Jia M, Yan S, Tian S, Zhu W, Zhou Z Abstract As an agricultural fungicide, penconazole (PEN) is widely used and has adverse effects on various organisms. In order to evaluate the ecological safety risks of PEN, the bioaccumulation and toxic effects of PEN in earthworms were studied. Specifically, the results show that the biota-sediment accumulation factor (BSAF) of PEN in earthworms reaches its maximum within 1 day, and then decreases slowly. It reached its lowest value after 14 days of PEN exposure and then rose again. In addition, oxidative stress and metabolic disorder of the earthworm with PEN exposure were assessed. After PEN exposure, the related indicators of oxidative stress involved in the activities of SOD and CAT and the contents of GSH and MDA all changed significantly in earthworms. Moreover, metabolomics analysis of earthworms showed disturbed metabolic profiles following PEN exposure. Respectively, PEN exposure significantly altered the relative abundances of 14 metabolites in earthworms. In general, exposure to PEN caused oxidative stress and metabolic profile disorders of earthworms. The results of this study will be helpful for further evaluation of soil ecological security of PEN. PMID: 32621186 [PubMed - as supplied by publisher]

Probabilistic identification of saccharide moieties in biomolecules and their protein complexes.

Mon, 06/07/2020 - 14:10
Related Articles Probabilistic identification of saccharide moieties in biomolecules and their protein complexes. Sci Data. 2020 Jul 03;7(1):210 Authors: Dashti H, Westler WM, Wedell JR, Demler OV, Eghbalnia HR, Markley JL, Mora S Abstract The chemical composition of saccharide complexes underlies their biomedical activities as biomarkers for cardiometabolic disease, various types of cancer, and other conditions. However, because these molecules may undergo major structural modifications, distinguishing between compounds of saccharide and non-saccharide origin becomes a challenging computational problem that hinders the aggregation of information about their bioactive moieties. We have developed an algorithm and software package called "Cheminformatics Tool for Probabilistic Identification of Carbohydrates" (CTPIC) that analyzes the covalent structure of a compound to yield a probabilistic measure for distinguishing saccharides and saccharide-derivatives from non-saccharides. CTPIC analysis of the RCSB Ligand Expo (database of small molecules found to bind proteins in the Protein Data Bank) led to a substantial increase in the number of ligands characterized as saccharides. CTPIC analysis of Protein Data Bank identified 7.7% of the proteins as saccharide-binding. CTPIC is freely available as a webservice at (http://ctpic.nmrfam.wisc.edu). PMID: 32620933 [PubMed - as supplied by publisher]

Metabolome of Mammary Tumors Differs from Normal Mammary Glands But Is Not Altered by Time-restricted Feeding Under Obesogenic Conditions.

Mon, 06/07/2020 - 14:10
Related Articles Metabolome of Mammary Tumors Differs from Normal Mammary Glands But Is Not Altered by Time-restricted Feeding Under Obesogenic Conditions. Anticancer Res. 2020 Jul;40(7):3697-3705 Authors: Yan L, Sundaram S, Rust BM, Picklo MJ, Bukowski MR Abstract BACKGROUND/AIM: Time restricted feeding (TRF) mitigates the high-fat diet-enhanced mammary tumorigenesis in a MMTV-PyMT breast cancer model. MATERIALS AND METHODS: We performed untargeted metabolomic and targeted transcriptomic analyses on mammary tumors from MMTV-PyMT mice fed a standard AIN93G diet, a high-fat diet (HFD), or HFD with TRF (12 h, dark phase) and mammary glands from wild-type mice fed the AIN93G diet. RESULTS: The metabolic profile of mammary tumors differed from that of mammary glands; there was no impact of TRF upon tumor metabolome. TRF did reduce elevated expression of Hmgcr, Srebp1, Fads2, and Ppard in mammary tumors, indicating a down-regulation of lipid metabolism. CONCLUSION: The null effect of TRF on the metabolomic profile does not rule out changes in more refined intracellular signaling pathways. It suggests that the protection of TRF against mammary tumorigenesis may rely upon its action on the host rather than a direct effect on tumor metabolism. PMID: 32620608 [PubMed - as supplied by publisher]

A novel urinary biomarker protein panel to identify children with ureteropelvic junction obstruction - A pilot study.

Mon, 06/07/2020 - 14:10
Related Articles A novel urinary biomarker protein panel to identify children with ureteropelvic junction obstruction - A pilot study. J Pediatr Urol. 2020 Jun 11;: Authors: Devarakonda CKV, Shearier ER, Hu C, Grady J, Balsbaugh JL, Makari JH, Ferrer FA, Shapiro LH Abstract INTRODUCTION AND OBJECTIVE: Reliable urinary biomarker proteins would be invaluable in identifying children with ureteropelvic junction obstruction (UPJO) as the existing biomarker proteins are inconsistent in their predictive ability. Therefore, the aim of this study was to identify consistent and reliable urinary biomarker proteins in children with UPJO. METHODS: To identify candidate biomarker proteins, total protein from age-restricted (<2 years) and sex-matched (males) control (n = 22) and UPJO (n = 21) urine samples was analyzed by mass spectrometry. Proteins that were preferentially identified in UPJO samples were selected (2-step process) and ranked according to their diagnostic odds ratio value. The top ten proteins with highest odds ratio values were selected and tested individually by ELISA. The total amount of each protein was normalized to urine creatinine and the median with interquartile ranges for control and UPJO samples was determined. Additionally, fold change (UPJO/Control) of medians of the final panel of 5 proteins was also determined. Finally, we calculated the average + 3(SD) and average + 4(SD) values of each of the 5 proteins in the control samples and used it as an arbitrary cutoff to classify individual control and UPJO samples. RESULTS: In the first step of our selection process, we identified 171 proteins in UPJO samples that were not detected in the majority of the control samples (16/22 samples, or 72.7%). Of the 171 proteins, only 50 proteins were detected in at least 11/21 (52.4%) of the UPJO samples and hence were selected in the second step. Subsequently, these 50 proteins were ranked according to the odds ratio value and the top 10 ranked proteins were validated by ELISA. Five of the 10 proteins - prostaglandin-reductase-1, ficolin-2, nicotinate-nucleotide pyrophosphorylase [carboxylating], immunoglobulin superfamily-containing leucine-rich-repeat-protein and vascular cell adhesion molecule-1 were present at higher levels in the UPJO samples (fold-change of the median protein concentrations ranging from 2.9 to 9.4) and emerged as a panel of biomarkers to identify obstructive uropathy. Finally, the order of prevalence of the 5 proteins in UPJO samples is PTGR1>FCN2>QPRT>ISLR>VCAM1. CONCLUSION: In summary, this unique screening strategy led to the identification of previously unknown biomarker proteins that when screened collectively, may reliably distinguish between obstructed vs. non-obstructed infants and may prove useful in identifying informative biomarker panels for biological samples from many diseases. PMID: 32620509 [PubMed - as supplied by publisher]

Oxidative Stress and Redox-Modulating Therapeutics in Inflammatory Bowel Disease.

Mon, 06/07/2020 - 14:10
Related Articles Oxidative Stress and Redox-Modulating Therapeutics in Inflammatory Bowel Disease. Trends Mol Med. 2020 Jun 30;: Authors: Bourgonje AR, Feelisch M, Faber KN, Pasch A, Dijkstra G, van Goor H Abstract Inflammatory bowel disease (IBD) is associated with the production of reactive species that target cysteine redox switches in proteins, thereby affecting gene regulation, DNA damage, ion transport, intermediary metabolism, and mitochondrial function. Precursors of reactive species are derived from organic and inorganic compounds and their cofactors, including amino acids, vitamins, oxygen, nitrite, and sulfate. Nutrition and the gut microbiome fuel this process to a significant extent. The production of reactive species in IBD is reflected by a reduction in systemic free thiols, the major components of the antioxidant machinery. Systemic free thiols are amenable to nutritional or therapeutic intervention. This opens up future avenues for therapeutic modulation of redox status in IBD. PMID: 32620502 [PubMed - as supplied by publisher]

Plasma high-resolution metabolomics identifies linoleic acid and linked metabolic pathways associated with bone mineral density.

Mon, 06/07/2020 - 14:10
Related Articles Plasma high-resolution metabolomics identifies linoleic acid and linked metabolic pathways associated with bone mineral density. Clin Nutr. 2020 Jun 04;: Authors: Bellissimo MP, Ziegler TR, Jones DP, Liu KH, Fernandes J, Roberts JL, Weitzmann MN, Pacifici R, Alvarez JA Abstract BACKGROUND & AIMS: There is a considerable degree of variation in bone mineral density (BMD) within populations. Use of plasma metabolomics may provide insight into established and novel determinants of BMD variance, such as nutrition and gut microbiome composition, to inform future prevention and treatment strategies for loss of BMD. Using high-resolution metabolomics (HRM), we examined low-molecular weight plasma metabolites and nutrition-related metabolic pathways associated with BMD. METHODS: This cross-sectional study included 179 adults (mean age 49.5 ± 10.3 yr, 64% female). Fasting plasma was analyzed using ultra-high-resolution mass spectrometry with liquid chromatography. Whole body and spine BMD were assessed by dual energy X-ray absorptiometry and expressed as BMD (g/cm2) or Z-scores. Multiple linear regression, pathway enrichment, and module analyses were used to determine key plasma metabolic features associated with bone density. RESULTS: Of 10,210 total detected metabolic features, whole body BMD Z-score was associated with 710 metabolites, which were significantly enriched in seven metabolic pathways, including linoleic acid, fatty acid activation and biosynthesis, and glycerophospholipid metabolism. Spine BMD was associated with 970 metabolites, significantly enriched in pro-inflammatory pathways involved in prostaglandin formation and linoleic acid metabolism. In module analyses, tryptophan- and polyamine-derived metabolites formed a network that was significantly associated with spine BMD, supporting a link with the gut microbiome. CONCLUSIONS: Plasma HRM provides comprehensive information relevant to nutrition and components of the microbiome that influence bone health. This data supports pro-inflammatory fatty acids and the gut microbiome as novel regulators of postnatal bone remodeling. PMID: 32620447 [PubMed - as supplied by publisher]

Sparse reduced-rank regression for integrating omics data.

Mon, 06/07/2020 - 14:10
Related Articles Sparse reduced-rank regression for integrating omics data. BMC Bioinformatics. 2020 Jul 03;21(1):283 Authors: Hilafu H, Safo SE, Haine L Abstract BACKGROUND: The problem of assessing associations between multiple omics data including genomics and metabolomics data to identify biomarkers potentially predictive of complex diseases has garnered considerable research interest nowadays. A popular epidemiology approach is to consider an association of each of the predictors with each of the response using a univariate linear regression model, and to select predictors that meet a priori specified significance level. Although this approach is simple and intuitive, it tends to require larger sample size which is costly. It also assumes variables for each data type are independent, and thus ignores correlations that exist between variables both within each data type and across the data types. RESULTS: We consider a multivariate linear regression model that relates multiple predictors with multiple responses, and to identify multiple relevant predictors that are simultaneously associated with the responses. We assume the coefficient matrix of the responses on the predictors is both row-sparse and of low-rank, and propose a group Dantzig type formulation to estimate the coefficient matrix. CONCLUSION: Extensive simulations demonstrate the competitive performance of our proposed method when compared to existing methods in terms of estimation, prediction, and variable selection. We use the proposed method to integrate genomics and metabolomics data to identify genetic variants that are potentially predictive of atherosclerosis cardiovascular disease (ASCVD) beyond well-established risk factors. Our analysis shows some genetic variants that increase prediction of ASCVD beyond some well-established factors of ASCVD, and also suggest a potential utility of the identified genetic variants in explaining possible association between certain metabolites and ASCVD. PMID: 32620072 [PubMed - as supplied by publisher]

metabolomics; +24 new citations

Sun, 05/07/2020 - 23:06
24 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 2020/07/05PubMed 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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