Dataset Information

Correlations Between LC-MS/MS-Detected Glycomics and NMR-Detected Metabolomics in Caenorhabditis elegans Development.

ABSTRACT: This study examined the relationship between glycans, metabolites, and development in C. elegans. Samples of N2 animals were synchronized and grown to five different time points ranging from L1 to a mixed population of adults, gravid adults, and offspring. Each time point was replicated seven times. The samples were each assayed by a large particle flow cytometer (Biosorter) for size distribution data, LC-MS/MS for targeted N- and O-linked glycans, and NMR for metabolites. The same samples were utilized for all measurements, which allowed for statistical correlations between the data. A new protocol was developed to correlate Biosorter developmental data with LC-MS/MS data to obtain stage-specific information of glycans. From the five time points, four distinct sizes of worms were observed from the Biosorter distributions, ranging from the smallest corresponding to L1 to adult animals. A network model was constructed using the four binned sizes of worms as starting nodes and adding glycans and metabolites that had correlations with r ? 0.5 to those nodes. The emerging structure of the network showed distinct patterns of N- and O-linked glycans that were consistent with previous studies. Furthermore, some metabolites that were correlated to these glycans and worm sizes showed interesting interactions. Of note, UDP-GlcNAc had strong positive correlations with many O-glycans that were expressed in the largest animals. Similarly, phosphorylcholine correlated with many N-glycans that were expressed in L1 animals.

SUBMITTER: Sheikh MO

PROVIDER: S-EPMC6611444 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Correlations Between LC-MS/MS-Detected Glycomics and NMR-Detected Metabolomics in Caenorhabditis elegans Development.

Sheikh M Osman MO Tayyari Fariba F Zhang Sicong S Judge Michael T MT Weatherly D Brent DB Ponce Francesca V FV Wells Lance L Edison Arthur S AS

Frontiers in molecular biosciences 20190628

This study examined the relationship between glycans, metabolites, and development in C. elegans. Samples of N2 animals were synchronized and grown to five different time points ranging from L1 to a mixed population of adults, gravid adults, and offspring. Each time point was replicated seven times. The samples were each assayed by a large particle flow cytometer (Biosorter) for size distribution data, LC-MS/MS for targeted N- and O-linked glycans, and NMR for metabolites. T ...[more]

PMID: 31316996

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Project description:BackgroundEsophageal adenocarcinoma (EAC) is a rarely curable disease and is rapidly rising worldwide in incidence. Barret's esophagus (BE) and high-grade dysplasia (HGD) are considered major risk factors for invasive adenocarcinoma. In the current study, unbiased global metabolic profiling methods were applied to serum samples from patients with EAC, BE and HGD, and healthy individuals, in order to identify metabolite based biomarkers associated with the early stages of EAC with the goal of improving prognostication.Methodology/principal findingsSerum metabolite profiles from patients with EAC (n?=?67), BE (n?=?3), HGD (n?=?9) and healthy volunteers (n?=?34) were obtained using high performance liquid chromatography-mass spectrometry (LC-MS) methods. Twelve metabolites differed significantly (p<0.05) between EAC patients and healthy controls. A partial least-squares discriminant analysis (PLS-DA) model had good accuracy with the area under the receiver operative characteristic curve (AUROC) of 0.82. However, when the results of LC-MS were combined with 8 metabolites detected by nuclear magnetic resonance (NMR) in a previous study, the combination of NMR and MS detected metabolites provided a much superior performance, with AUROC?=?0.95. Further, mean values of 12 of these metabolites varied consistently from healthy controls to the high-risk individuals (BE and HGD patients) and EAC subjects. Altered metabolic pathways including a number of amino acid pathways and energy metabolism were identified based on altered levels of numerous metabolites.Conclusions/significanceMetabolic profiles derived from the combination of LC-MS and NMR methods readily distinguish EAC patients and potentially promise important routes to understanding the carcinogenesis and detecting the cancer. Differences in the metabolic profiles between high-risk individuals and the EAC indicate the possibility of identifying the patients at risk much earlier to the development of the cancer.

Project description:Idiopathic REM sleep behavior disorder (iRBD) is now considered a prodromal stage of an α-synucleinopathy-related to neurodegenerative disease such as Parkinson's diseases. Emerging evidence has shown that post-translational modification or glycosylation are implicated in dynamic disease mechanisms and the onset of many pathological conditions. We hypothesized that the characterization of the glycosylation pattern of patients with RBD would be of great value to understand the pathophysiology and underlying mechanisms and represent potentially useful biomarkers for disease-associated molecular changes. To test this hypothesis, we assessed the serum glycome of patients with RBD and compared to that of healthy controls. NanoRPLC-MS was used to generate quantitative N-glycan profiles while high-temperature PGC-LC-MS platform was employed to generate quantitative isomeric N-glycan profiles. By analyzing permethylated glycans derived from human blood sera on C18-LC-MS/MS, we identified 59 N-glycan structures in healthy (control) cohort, 56 N-glycans in RBD cohort. Sixteen N-glycans structures were found to be significantly altered in the RBD cohort (p < 0.05). N-glycans with the composition of HexNAc4 Hex5 Fuc1 , HexNAc5 Hex5 , and HexNAc4 Hex5 Fuc1 NeuAc1 presented the most substantial difference between controls and RBD patients (p < 0.01). HexNAc4 Hex5 Fuc1 NeuAc1 showed a relatively high abundance (3.1 ± 0.7% in the control cohort versus 4 ± 3% in the idiopathic RBD cohort). These N-glycans can be potential diagnostic biomarker candidates and provide a window into underlying neurodegenerative processes in patients with idiopathic RBD. In addition, 7 N-glycan isomers were significantly different between controls and RBD patients (p < 0.05). HexNAc4 Hex5 Fuc1 NeuAc1 (4511-2) and HexNAc4 Hex5 Fuc1 NeuAc2 (4512-2) showed the most substantial difference between the control and idiopathic RBD cohorts (p < 0.001). Levels of both these two isomeric structures were higher in the idiopathic RBD cohort. Further larger studies are required to assess the reproducibility of these findings and to elucidate the role played by the changes in glycan structures in the pathogenetic mechanisms of RBD. This information will be instrumental in developing molecular therapeutic targets to promote neuroprotection and prevention of neurodegeneration.

Dataset Information

Correlations Between LC-MS/MS-Detected Glycomics and NMR-Detected Metabolomics in Caenorhabditis elegans Development.

Publications

Correlations Between LC-MS/MS-Detected Glycomics and NMR-Detected Metabolomics in <i>Caenorhabditis elegans</i> Development.

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