Dataset Information

Integration of targeted metabolomics and transcriptomics identifies deregulation of phosphatidylcholine metabolism in Huntington's disease peripheral blood samples.

ABSTRACT:

Introduction

Metabolic changes have been frequently associated with Huntington's disease (HD). At the same time peripheral blood represents a minimally invasive sampling avenue with little distress to Huntington's disease patients especially when brain or other tissue samples are difficult to collect.

Objectives

We investigated the levels of 163 metabolites in HD patient and control serum samples in order to identify disease related changes. Additionally, we integrated the metabolomics data with our previously published next generation sequencing-based gene expression data from the same patients in order to interconnect the metabolomics changes with transcriptional alterations.

Methods

This analysis was performed using targeted metabolomics and flow injection electrospray ionization tandem mass spectrometry in 133 serum samples from 97 Huntington's disease patients (29 pre-symptomatic and 68 symptomatic) and 36 controls.

Results

By comparing HD mutation carriers with controls we identified 3 metabolites significantly changed in HD (serine and threonine and one phosphatidylcholine-PC ae C36:0) and an additional 8 phosphatidylcholines (PC aa C38:6, PC aa C36:0, PC ae C38:0, PC aa C38:0, PC ae C38:6, PC ae C42:0, PC aa C36:5 and PC ae C36:0) that exhibited a significant association with disease severity. Using workflow based exploitation of pathway databases and by integrating our metabolomics data with our gene expression data from the same patients we identified 4 deregulated phosphatidylcholine metabolism related genes (ALDH1B1, MBOAT1, MTRR and PLB1) that showed significant association with the changes in metabolite concentrations.

Conclusion

Our results support the notion that phosphatidylcholine metabolism is deregulated in HD blood and that these metabolite alterations are associated with specific gene expression changes.

SUBMITTER: Mastrokolias A

PROVIDER: S-EPMC4963448 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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Publications

Integration of targeted metabolomics and transcriptomics identifies deregulation of phosphatidylcholine metabolism in Huntington's disease peripheral blood samples.

Mastrokolias Anastasios A Pool Rene R Mina Eleni E Hettne Kristina M KM van Duijn Erik E van der Mast Roos C RC van Ommen GertJan G 't Hoen Peter A C PA Prehn Cornelia C Adamski Jerzy J van Roon-Mom Willeke W

Metabolomics : Official journal of the Metabolomic Society 20160727

<h4>Introduction</h4>Metabolic changes have been frequently associated with Huntington's disease (HD). At the same time peripheral blood represents a minimally invasive sampling avenue with little distress to Huntington's disease patients especially when brain or other tissue samples are difficult to collect.<h4>Objectives</h4>We investigated the levels of 163 metabolites in HD patient and control serum samples in order to identify disease related changes. Additionally, we integrated the metabol ...[more]

PMID: 27524956

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Project description:Skeletal muscle is an important economic trait in duck breeding; however, little is known about the molecular mechanisms of its embryonic development. Here, the transcriptomes and metabolomes of breast muscle of Pekin duck from 15 (E15_BM), 21 (E21_BM), and 27 (E27_BM) days of incubation were compared and analyzed. The metabolome results showed that the differentially accumulated metabolites (DAMs), including the up-regulated metabolites, l-glutamic acid, n-acetyl-1-aspartylglutamic acid, l-2-aminoadipic acid, 3-hydroxybutyric acid, bilirubin, and the significantly down-regulated metabolites, palmitic acid, 4-guanidinobutanoate, myristic acid, 3-dehydroxycarnitine, and s-adenosylmethioninamine, were mainly enriched in metabolic pathways, biosynthesis of secondary metabolites, biosynthesis of cofactors, protein digestion and absorption, and histidine metabolism, suggesting that these pathways may play important roles in the muscle development of duck during the embryonic stage. Moreover, a total of 2142 (1552 up-regulated and 590 down-regulated), 4873 (3810 up-regulated and 1063 down-regulated), and 2401 (1606 up-regulated and 795 down-regulated) DEGs were identified from E15_BM vs. E21_BM, E15_BM vs. E27_BM and E21_BM vs. E27_BM in the transcriptome, respectively. The significantly enriched GO terms from biological processes were positive regulation of cell proliferation, regulation of cell cycle, actin filament organization, and regulation of actin cytoskeleton organization, which were associated with muscle or cell growth and development. Seven significant pathways, highly enriched by FYN, PTK2, PXN, CRK, CRKL, PAK, RHOA, ROCK, INSR, PDPK1, and ARHGEF, were focal adhesion, regulation of actin cytoskeleton, wnt signaling pathway, insulin signaling pathway, extracellular matrix (ECM)-receptor interaction, cell cycle, and adherens junction, which participated in regulating the development of skeletal muscle in Pekin duck during the embryonic stage. KEGG pathway analysis of the integrated transcriptome and metabolome indicated that the pathways, including arginine and proline metabolism, protein digestion and absorption, and histidine metabolism, were involved in regulating skeletal muscle development in embryonic Pekin duck. These findings suggested that the candidate genes and metabolites involved in crucial biological pathways may regulate muscle development in the Pekin duck at the embryonic stage, and increased our understanding of the molecular mechanisms underlying the avian muscle development.

Dataset Information

Integration of targeted metabolomics and transcriptomics identifies deregulation of phosphatidylcholine metabolism in Huntington's disease peripheral blood samples.

Introduction

Objectives

Methods

Results

Conclusion

Publications

Integration of targeted metabolomics and transcriptomics identifies deregulation of phosphatidylcholine metabolism in Huntington's disease peripheral blood samples.

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