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

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PubMed
NCBI: db=pubmed; Term=metabolomics
Updated: 25 min 41 sec ago

Skeletal muscle interstitial fluid metabolomics at rest and associated with an exercise bout: application in rats and humans.

Wed, 07/11/2018 - 13:55
Related Articles Skeletal muscle interstitial fluid metabolomics at rest and associated with an exercise bout: application in rats and humans. Am J Physiol Endocrinol Metab. 2018 Nov 06;: Authors: Zhang J, Bhattacharyya S, Hickner RC, Light AR, Lambert CJ, Gale BK, Fiehn O, Adams SH Abstract Blood or biopsies are often applied to characterize metabolites that are modulated by exercising muscle. However, blood has inputs derived from multiple tissues, biopsies cannot discriminate secreted vs. intracellular metabolites and their invasive nature is challenging for frequent collections in sensitive populations (e.g., children, pregnant women). Thus, minimally-invasive approaches to interstitial fluid (IF) metabolomics would be valuable. A catheter was designed to collect gastrocnemius IF from acutely anesthetized adult male rats, at rest or immediately following 20 min. exercise (~60% V̇O2max). Using non-targeted, gas chromatography/time-of-flight mass spectrometry analysis, 299 metabolites were detected, including non-annotated metabolites, sugars, fatty acids, amino acids, purine metabolites and derivatives. Just 43% of all detected metabolites were in common between IF and blood plasma, and only 20% of exercise-modified metabolites were shared in both pools, highlighting that the blood does not fully reflect the metabolic outcomes in muscle. Notable exercise patterns included increased IF amino acids (except Leu and Isoleu), increased α-ketoglutarate and citrate (which may reflect tricarboxylic acid cataplerosis or shifts in non-mitochondrial pathways), and higher concentration of the signaling lipid oleamide. A preliminary study of human muscle IF was conducted using a 20 kDa microdialysis catheter placed in the vastus lateralis of 5 healthy adults at rest and during exercise (60% V̇O2max, 30 min). Approximately 70% of commonly-detected metabolites discriminating rest and exercise in rats were also changed in exercising humans. Interstitium metabolomics may aid in the identification of molecules that signal muscle work (e.g., exertion, fatigue) and muscle health. PMID: 30398905 [PubMed - as supplied by publisher]

Alleviating the Neglected Tropical Diseases: Recent Developments in Diagnostics and Detection.

Wed, 07/11/2018 - 13:55
Related Articles Alleviating the Neglected Tropical Diseases: Recent Developments in Diagnostics and Detection. Curr Top Med Chem. 2018 Nov 06;: Authors: Hazra S, Patra S Abstract Background Neglected tropical diseases (NTDs) are communicable diseases caused by a group of bacteria, viruses, protozoa and helminths prevalent in more than 145 countries that affect the world's poverty stricken populations. WHO enlists 18 NTDs amongst people living in endemic areas having inaccessibility to preventive measures. Steps to reduce the global disease burden of the NTDs need attention at multi-factorial levels. Control programmes, mass drug administrations, transmission checks, eradication surveillances and diagnoses are some of them. The foremost in this list is confirmatory diagnosis. A comprehensive summary of the innovative, high-impact, multiplexed, low-cost diagnostic tools developed in the last decade that helped to meet the needs of users can depict a holistic approach to further evaluate potential technologies and reagents currently in research. Major advancements A literature survey based on developing nano-biotechnological platforms to meet the diagnostic challenges in NTDs towards development of a useful point-of-care (POC) unit is reported. However, in order to pave the way for complete eradication more sensitive tools are required that are user-friendly and applicable for use in endemic and low-resource settings. There are various novel research progresses/advancements made for qualitative and quantitative measurement of infectious load in some diseases like dengue, Chagas disease and leishmaniasis; though further improvements on the specificity and sensitivity front are still awaited. Strategies to combat the problem of antimicrobial drug resistance in diagnosis of NTDs have also been put forward by various research groups and organizations. Moreover, the state-of-the-art "omics" approaches like metabolomics and metagenomics have also started to contribute constructively towards diagnosis and prevention of the NTDs. Conclusion A concrete solution towards a single specimen based common biomarker detection platform for NTDs is lacking. Identifying robust biomarkers and implementing them on simple diagnostic tools to ease the process of pathogen detection can help us understand the obstacles in current diagnostic measures of the NTDs. PMID: 30398115 [PubMed - as supplied by publisher]

Integrating metabolomics with genomics.

Wed, 07/11/2018 - 13:55
Related Articles Integrating metabolomics with genomics. Pharmacogenomics. 2018 Nov 06;: Authors: Telenti A PMID: 30398072 [PubMed - as supplied by publisher]

The Changes of Serum Metabolites in Diabetic GK Rats after Ileal Transposition Surgery.

Wed, 07/11/2018 - 13:55
Related Articles The Changes of Serum Metabolites in Diabetic GK Rats after Ileal Transposition Surgery. Obes Surg. 2018 Nov 06;: Authors: Yan K, Chen W, Zhu H, Lin G, Sun W, Liu X, Pan H, Wang L, Yang H, Liu M, Gong F Abstract BACKGROUND: Ileal transposition (IT) surgery could improve metabolism. Metabolomics has been applied comprehensively in analyzing the global dynamic alterations of metabolites. In the present study, we aimed to investigate serum metabolite alterations in diabetic Goto-Kakizaki (GK) rats after IT surgery. METHODS: Male GK rats were subjected to IT and Sham-IT surgery. Six weeks later, body weight, food intake, fat mass, and serum biochemical parameters were measured. The serum metabolomic fingerprint was analyzed using ultra-performance liquid chromatography-mass spectrometry (LC-MS)-based, non-targeted metabolomic approach. The differential metabolites were identified using principal component analysis and orthogonal partial least squares discriminant analysis. Metabolic pathway analysis was performed using HMDB and KEGG databases. RESULTS: The body weight, food intake, fat mass, serum levels of glucose and insulin, and homeostasis model assessment of insulin resistance (HOMA-IR) of IT rats were significantly decreased when compared with Sham-IT rats (all P < 0.05). In the metabolomics analysis, ten serum differential metabolites were identified. Compared with Sham-IT rats, serum LysoPC(O-18:0) and PG(20:4/20:0) of IT rats were decreased, while genistein 4'-O-glucuronide, 5,6:8,9-Diepoxyergost-22-ene-3,7beta-diol, PI(16:0/18:2(9Z,12Z)), docosapentaenoic acid, 3-Oxo-4,6-choladienoic acid, 3-Oxocholic acid, and TG were increased. Pathway analysis highlighted the following pathways: ether lipid metabolism, alpha linolenic acid and linolenic acid metabolism, incretin synthesis and secretion, free fatty acid receptors, and biosynthesis of unsaturated fatty acids. CONCLUSIONS: IT surgery could significantly decrease body weight and fat mass and improve glucose metabolism in diabetic GK rats. These beneficial effects might be related to the changes of serum metabolites which involved in lipid metabolism, bile acids, and incretin. PMID: 30397878 [PubMed - as supplied by publisher]

Partial loss of psychiatric risk gene Mir137 in mice causes repetitive behavior and impairs sociability and learning via increased Pde10a.

Wed, 07/11/2018 - 13:55
Related Articles Partial loss of psychiatric risk gene Mir137 in mice causes repetitive behavior and impairs sociability and learning via increased Pde10a. Nat Neurosci. 2018 Nov 05;: Authors: Cheng Y, Wang ZM, Tan W, Wang X, Li Y, Bai B, Li Y, Zhang SF, Yan HL, Chen ZL, Liu CM, Mi TW, Xia S, Zhou Z, Liu A, Tang GB, Liu C, Dai ZJ, Wang YY, Wang H, Wang X, Kang Y, Lin L, Chen Z, Xie N, Sun Q, Xie W, Peng J, Chen D, Teng ZQ, Jin P Abstract Genetic analyses have linked microRNA-137 (MIR137) to neuropsychiatric disorders, including schizophrenia and autism spectrum disorder. miR-137 plays important roles in neurogenesis and neuronal maturation, but the impact of miR-137 loss-of-function in vivo remains unclear. Here we show the complete loss of miR-137 in the mouse germline knockout or nervous system knockout (cKO) leads to postnatal lethality, while heterozygous germline knockout and cKO mice remain viable. Partial loss of miR-137 in heterozygous cKO mice results in dysregulated synaptic plasticity, repetitive behavior, and impaired learning and social behavior. Transcriptomic and proteomic analyses revealed that the miR-137 mRNA target, phosphodiesterase 10a (Pde10a), is elevated in heterozygous knockout mice. Treatment with the Pde10a inhibitor papaverine or knockdown of Pde10a ameliorates the deficits observed in the heterozygous cKO mice. Collectively, our results suggest that MIR137 plays essential roles in postnatal neurodevelopment and that dysregulation of miR-137 potentially contributes to neuropsychiatric disorders in humans. PMID: 30397325 [PubMed - as supplied by publisher]

Human-like hyperplastic prostate with low ZIP1 induced solely by Zn deficiency in rats.

Wed, 07/11/2018 - 13:55
Related Articles Human-like hyperplastic prostate with low ZIP1 induced solely by Zn deficiency in rats. Proc Natl Acad Sci U S A. 2018 Nov 05;: Authors: Fong LY, Jing R, Smalley KJ, Wang ZX, Taccioli C, Fan S, Chen H, Alder H, Huebner K, Farber JL, Fiehn O, Croce CM Abstract Prostate cancer is a leading cause of cancer death in men over 50 years of age, and there is a characteristic marked decrease in Zn content in the malignant prostate cells. The cause and consequences of this loss have thus far been unknown. We found that in middle-aged rats a Zn-deficient diet reduces prostatic Zn levels (P = 0.025), increases cellular proliferation, and induces an inflammatory phenotype with COX-2 overexpression. This hyperplastic/inflammatory prostate has a human prostate cancer-like microRNA profile, with up-regulation of the Zn-homeostasis-regulating miR-183-96-182 cluster (fold change = 1.41-2.38; P = 0.029-0.0003) and down-regulation of the Zn importer ZIP1 (target of miR-182), leading to a reduction of prostatic Zn. This inverse relationship between miR-182 and ZIP1 also occurs in human prostate cancer tissue, which is known for Zn loss. The discovery that the Zn-depleted middle-aged rat prostate has a metabolic phenotype resembling that of human prostate cancer, with a 10-fold down-regulation of citric acid (P = 0.0003), links citrate reduction directly to prostatic Zn loss, providing the underlying mechanism linking dietary Zn deficiency with miR-183-96-182 overexpression, ZIP1 down-regulation, prostatic Zn loss, and the resultant citrate down-regulation, changes mimicking features of human prostate cancer. Thus, dietary Zn deficiency during rat middle age produces changes that mimic those of human prostate carcinoma and may increase the risk for prostate cancer, supporting the need for assessment of Zn supplementation in its prevention. PMID: 30397150 [PubMed - as supplied by publisher]

Synthesis and degradation of FtsZ quantitatively predict the first cell division in starved bacteria.

Wed, 07/11/2018 - 13:55
Related Articles Synthesis and degradation of FtsZ quantitatively predict the first cell division in starved bacteria. Mol Syst Biol. 2018 Nov 05;14(11):e8623 Authors: Sekar K, Rusconi R, Sauls JT, Fuhrer T, Noor E, Nguyen J, Fernandez VI, Buffing MF, Berney M, Jun S, Stocker R, Sauer U Abstract In natural environments, microbes are typically non-dividing and gauge when nutrients permit division. Current models are phenomenological and specific to nutrient-rich, exponentially growing cells, thus cannot predict the first division under limiting nutrient availability. To assess this regime, we supplied starving Escherichia coli with glucose pulses at increasing frequencies. Real-time metabolomics and microfluidic single-cell microscopy revealed unexpected, rapid protein, and nucleic acid synthesis already from minuscule glucose pulses in non-dividing cells. Additionally, the lag time to first division shortened as pulsing frequency increased. We pinpointed division timing and dependence on nutrient frequency to the changing abundance of the division protein FtsZ. A dynamic, mechanistic model quantitatively relates lag time to FtsZ synthesis from nutrient pulses and FtsZ protease-dependent degradation. Lag time changed in model-congruent manners, when we experimentally modulated the synthesis or degradation of FtsZ. Thus, limiting abundance of FtsZ can quantitatively predict timing of the first cell division. PMID: 30397005 [PubMed - in process]

How to safeguard an appropriate "all trans retinoic acid" concentration to keep cell division on track: Exploring therapeutic hotspots from metabolomics.

Wed, 07/11/2018 - 13:55
Related Articles How to safeguard an appropriate "all trans retinoic acid" concentration to keep cell division on track: Exploring therapeutic hotspots from metabolomics. Med Hypotheses. 2018 Dec;121:56 Authors: Jayasooriya AP Abstract In this letter to editor, I hypothesize a potential affinity of retinol saturase (RetSat) enzyme towards a conjugated trienoic fatty acid; alpha-eleostearic acid (α-ESA) and subsequent hindrance of the action on its usual substrate; all trans retinol. Hence, RetSat is speculated to be involved in a rapid unusual conversion of α-ESA to conjugated linoleic acid (CLA), giving a less priority to its usual substrate all trans retinol, which would subsequently be converted into "all trans retinoic acid" (atRA). Otherwise, all trans retinol is converted by RetSat into all-trans-13,14-dihydroretinol and eventually forms all-trans-13,14-dihydroretinoic acid, but not the atRA. The atRA controls differentiation, proliferation and apoptosis of cells and it's deficiencies end up as neoplasms. Thus, here it is emphasized that safeguarding atRA would help controlling cell division and growth in a favourable manner. Hence, inhibition of RetSat could be a hot target to control unwarranted cell growths within the body. This hypothesis could be easily tested in a RetSat ablated (RetSat -/-) animal model or using antagonists on RetSat activity or α-ESA. PMID: 30396492 [PubMed - in process]

Volatile metabolomic signature of human breast cancer cell lines.

Wed, 07/11/2018 - 13:55
Related Articles Volatile metabolomic signature of human breast cancer cell lines. Sci Rep. 2017 03 03;7:43969 Authors: Silva CL, Perestrelo R, Silva P, Tomás H, Câmara JS Abstract Breast cancer (BC) remains the most prevalent oncologic pathology in women, causing huge psychological, economic and social impacts on our society. Currently, the available diagnostic tools have limited sensitivity and specificity. Metabolome analysis has emerged as a powerful tool for obtaining information about the biological processes that occur in organisms, and is a useful platform for discovering new biomarkers or make disease diagnosis using different biofluids. Volatile organic compounds (VOCs) from the headspace of cultured BC cells and normal human mammary epithelial cells, were collected by headspace solid-phase microextraction (HS-SPME) and analyzed by gas chromatography combined with mass spectrometry (GC-MS), thus defining a volatile metabolomic signature. 2-Pentanone, 2-heptanone, 3-methyl-3-buten-1-ol, ethyl acetate, ethyl propanoate and 2-methyl butanoate were detected only in cultured BC cell lines. Multivariate statistical methods were used to verify the volatomic differences between BC cell lines and normal cells in order to find a set of specific VOCs that could be associated with BC, providing comprehensive insight into VOCs as potential cancer biomarkers. The establishment of the volatile fingerprint of BC cell lines presents a powerful approach to find endogenous VOCs that could be used to improve the BC diagnostic tools and explore the associated metabolomic pathways. PMID: 28256598 [PubMed - indexed for MEDLINE]

Hepatocyte-secreted extracellular vesicles modify blood metabolome and endothelial function by an arginase-dependent mechanism.

Wed, 07/11/2018 - 13:55
Related Articles Hepatocyte-secreted extracellular vesicles modify blood metabolome and endothelial function by an arginase-dependent mechanism. Sci Rep. 2017 02 17;7:42798 Authors: Royo F, Moreno L, Mleczko J, Palomo L, Gonzalez E, Cabrera D, Cogolludo A, Vizcaino FP, van-Liempd S, Falcon-Perez JM Abstract Hepatocytes release extracellular vesicles (EVs) loaded with signaling molecules and enzymes into the bloodstream. Although the importance of EVs in the intercellular communication is already recognized, the metabolic impact of the enzymes carried by these vesicles is still unclear. We evaluated the global effect of the enzymatic activities of EVs by performing untargeted metabolomic profiling of serum samples after their exposure to EVs. This approach revealed a significant change in the abundance of 94 serum metabolic signals. Our study shows that these vesicles modify the concentration of metabolites of different chemical nature including metabolites related to arginine metabolism, which regulates vascular function. To assess the functional relevance of this finding, we examined the levels of arginase-1 protein and its activity in the hepatic EVs carrying the exosomal markers CD81 and CD63. Remarkably, the arginase activity was also detected in EVs isolated from the serum in vivo, and this vesicular activity significantly increased under liver-damaging conditions. Finally, we demonstrated that EVs secreted by hepatocytes inhibited the acetylcholine-induced relaxation in isolated pulmonary arteries, via an arginase-dependent mechanism. In summary, our study demonstrates that the hepatocyte-released EVs are metabolically active, affecting a number of serum metabolites involved in oxidative stress metabolism and the endothelial function. PMID: 28211494 [PubMed - indexed for MEDLINE]

metabolomics; +53 new citations

Tue, 06/11/2018 - 16:45
53 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 2018/11/06PubMed 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; +53 new citations

Tue, 06/11/2018 - 13:42
53 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 2018/11/06PubMed 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; +17 new citations

Mon, 05/11/2018 - 22:31
17 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 2018/11/05PubMed 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.

metabolomics; +17 new citations

Sat, 03/11/2018 - 12:16
17 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 2018/11/03PubMed 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.

Less SO2 residue may not indicate higher quality, better efficacy and weaker toxicity of sulfur-fumigated herbs: Ginseng, a pilot study.

Fri, 02/11/2018 - 12:00
Less SO2 residue may not indicate higher quality, better efficacy and weaker toxicity of sulfur-fumigated herbs: Ginseng, a pilot study. J Hazard Mater. 2018 Oct 22;364:376-387 Authors: Zhou SS, Hu JW, Kong M, Xu JD, Shen H, Chen HB, Shen MQ, Xu J, Li SL Abstract Sulfur dioxide (SO2) is a hazardous residue in sulfur-fumigated herbs. Standards limiting SO2 content have been adopted worldwide for quality control of sulfur-fumigated herbs, and herbs with less SO2 are believed to be better. However, the standards are based only on the safe dose of SO2 and may not characterize changes in herbal quality, thereby the efficacy and toxicity, resulting from sulfur fumigation. To confirm this, here the correlation of residual SO2 content with the quality/efficacy/toxicity of sulfur-fumigated herb was investigated, and ginseng was selected as a pilot study object. Four sulfur-fumigated ginseng samples with different SO2 contents were systemically compared regarding their quality, anti-inflammatory, anti-shock and anti-stress efficacies, as well as acute and chronic toxicities. The results demonstrated that the SO2 content did not correlate with the quality, efficacy and toxicity changes of ginseng; more specifically, less SO2 residue did not indicate higher quality, better efficacy nor weaker toxicity. This fact suggests that SO2 content cannot characterize the variations in quality, efficacy and toxicity of sulfur-fumigated herbs. Therefore, the standard limiting SO2 content alone may be inadequate for quality control of sulfur-fumigated herbs, and new standards including other indicators that can exactly reflect herbal efficacy and safety are necessary. PMID: 30384248 [PubMed - as supplied by publisher]

Concentrations of legacy and new contaminants are related to metabolite profiles in Hudson Bay polar bears.

Fri, 02/11/2018 - 12:00
Concentrations of legacy and new contaminants are related to metabolite profiles in Hudson Bay polar bears. Environ Res. 2018 Oct 11;168:364-374 Authors: Morris AD, Letcher RJ, Dyck M, Chandramouli B, Cosgrove J Abstract There are very few metabolomics assessments based on field accumulated, uncontrolled contaminant exposures in wildlife, particularly in the Arctic. In the present study, targeted metabolomics and contaminant data were analyzed together to assess potential influences of contaminant exposure on the hepatic metabolome of male polar bears (n = 29) from the southern and western Hudson Bay (SHB and WHB respectively), Canada. The 29 metabolites identified as important in the differentiation of the two subpopulations after partial least squares discriminant analysis (PLS-DA) included phosphatidylcholines (PCs), acylcarnitines (ACs; involved in β-oxidation of fatty acids), and the fatty acid (FA) arachidonic acid (ARA). Perfluorinated alkyl substances, polybrominated diphenyl ethers, dichlorodiphenyldichloroethylene (p,p'-DDE) and some highly chlorinated ortho-polychlorinated biphenyl congeners were greater in the SHB bears and were consistently inversely correlated with discriminating ACs and PCs between the subpopulations. The concentrations of discriminatory, legacy organochlorine pesticides along with one tetrachlorobiphenyl were greater in the WHB and were directly correlated with the VIP-identified ACs and PCs. ARA, glycerophospholipid and several amino acid metabolic pathways were identified as different between subpopulations and/or were impacted. ARA is an important, conditionally essential, dietary n-6 FA and is also part of the inflammation response, and elevated concentrations in the SHB could be related to differences in chronic contaminant exposure and/or differences in diet and/or season, among a number of possible explanations. Dietary tracers (stable isotopes of carbon and nitrogen) were correlated with some discriminatory metabolites, supporting the hypothesis that dietary variation was also an important factor in the differentiation of the subpopulations. The results suggest linkages between contaminant exposure in Hudson Bay polar bears and elements of the hepatic metabolome, particularly those related to lipid metabolism. PMID: 30384230 [PubMed - as supplied by publisher]

Serum metabolomics analysis of mice that received repeated airway exposure to a water-soluble PM2.5 extract.

Fri, 02/11/2018 - 12:00
Serum metabolomics analysis of mice that received repeated airway exposure to a water-soluble PM2.5 extract. Ecotoxicol Environ Saf. 2018 Oct 29;168:102-109 Authors: Zhao C, Niu M, Song S, Li J, Su Z, Wang Y, Gao Q, Wang H Abstract BACKGROUND: Air pollutant exposure negatively affects human health; however, the molecular mechanisms causing disease remain largely unclear. OBJECTIVES: To explore the effects of respiratory particulate matter (PM2.5) exposure on the serum metabolome and to identify biomarkers for risk assessment of PM2.5 exposure. METHODS: PM2.5 from Nanjing, China, was collected, and its water-soluble extract was subjected to component analysis. BALB/c mice received acute or prolonged exposure to insoluble PM2.5 particles or its water-soluble extract, and lung tissue was submitted to histopathological analyses. Serum samples were collected pre- and post-PM2.5 exposure and analyzed by liquid chromatography/mass spectrometry. RESULTS: Component analysis revealed that metals and inorganic ions were the most abundant components in the soluble PM2.5 samples. Acute exposure to insoluble PM2.5 particles and prolonged exposure to the water-soluble PM2.5 extract both induced severe lung injury, and the lung histopathological scores were significantly associated with PM2.5 exposure. Metabolomics analysis showed that prolonged exposure to the water-soluble PM2.5 extract was associated with statistically significant metabolite changes; the serum concentrations of 30 known metabolites, including metabolites of phospholipids, amino acids and sphingolipids, differed significantly between the control and PM2.5 exposure group. Pathway analysis identified an association of the tricarboxylic acid cycle (TCA) and the phospholipase metabolism pathway with PM2.5 exposure. The most influential metabolites for discriminating between the PM2.5-exposure group serum and the control serum were LysoPE, LysoPC, LGPC, citric acid, PAF C-18, NeuAcalpha2-3Galbeta-Cer, Lyso-PAF C-16, ganglioside GA2, 1-sn-glycero-3-phosphocholine, PC and L-tryptophan. CONCLUSIONS: Respiratory exposure to water-soluble PM2.5 extract has developmental consequences affecting not only the respiratory system but also metabolism. PMID: 30384157 [PubMed - as supplied by publisher]

Metabolomics in Systems Biology.

Fri, 02/11/2018 - 12:00
Metabolomics in Systems Biology. Adv Exp Med Biol. 2018;1102:51-68 Authors: Baharum SN, Azizan KA Abstract Over the last decade, metabolomics has continued to grow rapidly and is considered a dynamic technology in envisaging and elucidating complex phenotypes in systems biology area. The advantage of metabolomics compared to other omics technologies such as transcriptomics and proteomics is that these later omics only consider the intermediate steps in the central dogma pathway (mRNA and protein expression). Meanwhile, metabolomics reveals the downstream products of gene and expression of proteins. The most frequently used tools are nuclear magnetic resonance (NMR) spectroscopy and mass spectrometry (MS). Some of the common MS-based analyses are gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-mass spectrometry (LC-MS). These high-throughput instruments play an extremely crucial role in discovery metabolomics to generate data needed for further analysis. In this chapter, the concept of metabolomics in the context of systems biology is discussed and provides examples of its application in human disease studies, plant responses towards stress and abiotic resistance and also microbial metabolomics for biotechnology applications. Lastly, a few case studies of metabolomics analysis are also presented, for example, investigation of an aromatic herbal plant, Persicaria minor metabolome and microbial metabolomics for metabolic engineering applications. PMID: 30382568 [PubMed - in process]

Recent Development in Omics Studies.

Fri, 02/11/2018 - 12:00
Recent Development in Omics Studies. Adv Exp Med Biol. 2018;1102:1-9 Authors: Aizat WM, Ismail I, Noor NM Abstract The central dogma of molecular biology (DNA, RNA, protein and metabolite) has engraved our understanding of genetics in all living organisms. While the concept has been embraced for many decades, the development of high-throughput technologies particularly omics (genomics, transcriptomics, proteomics and metabolomics) has revolutionised the field to incorporate big data analysis including bioinformatics and systems biology as well as synthetic biology area. These omics approaches as well as systems and synthetic biology areas are now increasingly popular as seen by the growing numbers of publication throughout the years. Several journals which have published most of these related fields are also listed in this chapter to overview their impact and target journals. PMID: 30382565 [PubMed - in process]

Artificial Intelligence and amniotic fluid multiomics analysis: The prediction of perinatal outcome in asymptomatic short cervix.

Fri, 02/11/2018 - 12:00
Related Articles Artificial Intelligence and amniotic fluid multiomics analysis: The prediction of perinatal outcome in asymptomatic short cervix. Ultrasound Obstet Gynecol. 2018 Oct 31;: Authors: Bahado-Singh RO, Sonek J, McKenna D, Cool D, Aydas B, Turkoglu O, Bjorndahl T, Mandal R, Wishart D, Friedman P, Graham SF, Yilmaz A Abstract OBJECTIVE: To evaluate the utility of Artificial Intelligence i.e. Deep Learning (DL) and other machine learning techniques for the prediction of important pregnancy outcomes in asymptomatic short cervical length (CL). METHOD: The amniotic fluid (AF) had been obtained from second trimester patients with asymptomatic women with short cervical length (<15 mm). CL, funneling and the presence of AF 'sludge' were assessed in all cases. Combined targeted metabolomic and proteomic analysis of amniotic fluid (AF) was performed. A combination of liquid Chromatography -Mass spectrometry (LC-MS-MS and) and proton Nuclear Mass Spectrometry (1 H-NMR) -based metabolomics and targeted proteomics analysis (Bioplex Human cytokine Group-1 assay (Bio-Rad) consisting of chemokines, cytokines and growth factors, were performed on the AF samples. To determine the robustness of the markers we used multiple machine learning techniques including deep learning (DL) to predict moderate prematurity, <34 weeks, latency period prior to delivery, and NICU stay. Logistic regression analysis was also used. Omics biomarkers were evaluated alone and in combination with standard sonographic, clinical and demographic factors to predict outcome. Predictive accuracy was calculated using area under the receiver operating characteristics curve (AUC) and 95% CI, sensitivity and specificity values. RESULTS: Of a total of 32 patients in the study, complete omics analysis, demographic and clinical data and outcomes information was available in 26. Of these 11 (42.3%) of patients delivered at ≥ 34 weeks while 15 (57.7%) delivered < 34 weeks. There was no statistically significant difference in the CL (mean /SD CL 11.2 (4.40)mm versus 8.9 (5.30) mm, p=0.31. DL had an AUC (95%CI) of 0.89 (0.81-0.97) for delivery < 34 weeks gestation, 0.89 (0.79-0.99) for delivery < 28 days post -amniocentesis and 0.792 (0. 70-0.89) for NICU stay. These values were overall higher than for the other five machine learning methods. Each ML technique individually yielded statistically significantly prediction of the different perinatal outcomes. CONCLUSIONS: This is the first report using AI combined with proteomics , metabolomics and ultrasound assessment . Good to excellent prediction of important perinatal outcomes were achieved in asymptomatic mid-trimester CL shortening. AIM: The aim was to predict important perinatal outcomes in asymptomatic patients with shortened cervical length (CL) using Artificial intelligence analysis of amniotic fluid metabolomics and proteomics data. This article is protected by copyright. All rights reserved. PMID: 30381856 [PubMed - as supplied by publisher]

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