Integration of the transcriptome and glycome for identification of glycan cell signatures.

Abnormalities in glycan biosynthesis have been conclusively linked to many diseases but the complexity of glycosylation has hindered the analysis of glycan data in order to identify glycoforms contributing to disease. To overcome this limitation, we developed a quantitative N-glycosylation model tha...

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Autores principales: Sandra V Bennun, Kevin J Yarema, Michael J Betenbaugh, Frederick J Krambeck
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Publicado: Public Library of Science (PLoS) 2013
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spelling oai:doaj.org-article:cddeeac423a2421e825885b2eba762b72021-11-18T05:52:33ZIntegration of the transcriptome and glycome for identification of glycan cell signatures.1553-734X1553-735810.1371/journal.pcbi.1002813https://doaj.org/article/cddeeac423a2421e825885b2eba762b72013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23326219/pdf/?tool=EBIhttps://doaj.org/toc/1553-734Xhttps://doaj.org/toc/1553-7358Abnormalities in glycan biosynthesis have been conclusively linked to many diseases but the complexity of glycosylation has hindered the analysis of glycan data in order to identify glycoforms contributing to disease. To overcome this limitation, we developed a quantitative N-glycosylation model that interprets and integrates mass spectral and transcriptomic data by incorporating key glycosylation enzyme activities. Using the cancer progression model of androgen-dependent to androgen-independent Lymph Node Carcinoma of the Prostate (LNCaP) cells, the N-glycosylation model identified and quantified glycan structural details not typically derived from single-stage mass spectral or gene expression data. Differences between the cell types uncovered include increases in H(II) and Le(y) epitopes, corresponding to greater activity of α2-Fuc-transferase (FUT1) in the androgen-independent cells. The model further elucidated limitations in the two analytical platforms including a defect in the microarray for detecting the GnTV (MGAT5) enzyme. Our results demonstrate the potential of systems glycobiology tools for elucidating key glycan biomarkers and potential therapeutic targets. The integration of multiple data sets represents an important application of systems biology for understanding complex cellular processes.Sandra V BennunKevin J YaremaMichael J BetenbaughFrederick J KrambeckPublic Library of Science (PLoS)articleBiology (General)QH301-705.5ENPLoS Computational Biology, Vol 9, Iss 1, p e1002813 (2013)
institution DOAJ
collection DOAJ
language EN
topic Biology (General)
QH301-705.5
spellingShingle Biology (General)
QH301-705.5
Sandra V Bennun
Kevin J Yarema
Michael J Betenbaugh
Frederick J Krambeck
Integration of the transcriptome and glycome for identification of glycan cell signatures.
description Abnormalities in glycan biosynthesis have been conclusively linked to many diseases but the complexity of glycosylation has hindered the analysis of glycan data in order to identify glycoforms contributing to disease. To overcome this limitation, we developed a quantitative N-glycosylation model that interprets and integrates mass spectral and transcriptomic data by incorporating key glycosylation enzyme activities. Using the cancer progression model of androgen-dependent to androgen-independent Lymph Node Carcinoma of the Prostate (LNCaP) cells, the N-glycosylation model identified and quantified glycan structural details not typically derived from single-stage mass spectral or gene expression data. Differences between the cell types uncovered include increases in H(II) and Le(y) epitopes, corresponding to greater activity of α2-Fuc-transferase (FUT1) in the androgen-independent cells. The model further elucidated limitations in the two analytical platforms including a defect in the microarray for detecting the GnTV (MGAT5) enzyme. Our results demonstrate the potential of systems glycobiology tools for elucidating key glycan biomarkers and potential therapeutic targets. The integration of multiple data sets represents an important application of systems biology for understanding complex cellular processes.
format article
author Sandra V Bennun
Kevin J Yarema
Michael J Betenbaugh
Frederick J Krambeck
author_facet Sandra V Bennun
Kevin J Yarema
Michael J Betenbaugh
Frederick J Krambeck
author_sort Sandra V Bennun
title Integration of the transcriptome and glycome for identification of glycan cell signatures.
title_short Integration of the transcriptome and glycome for identification of glycan cell signatures.
title_full Integration of the transcriptome and glycome for identification of glycan cell signatures.
title_fullStr Integration of the transcriptome and glycome for identification of glycan cell signatures.
title_full_unstemmed Integration of the transcriptome and glycome for identification of glycan cell signatures.
title_sort integration of the transcriptome and glycome for identification of glycan cell signatures.
publisher Public Library of Science (PLoS)
publishDate 2013
url https://doaj.org/article/cddeeac423a2421e825885b2eba762b7
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AT kevinjyarema integrationofthetranscriptomeandglycomeforidentificationofglycancellsignatures
AT michaeljbetenbaugh integrationofthetranscriptomeandglycomeforidentificationofglycancellsignatures
AT frederickjkrambeck integrationofthetranscriptomeandglycomeforidentificationofglycancellsignatures
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