title: Integration of the transcriptome and glycome for identification of glycan cell signatures.
abstract: 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.
authors: Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, Maryland, United States of America. svbennun@gmail.com
authors: Sandra V
authors: SV
authors: Bennun
authors: Kevin J
authors: KJ
authors: Yarema
authors: Michael J
authors: MJ
authors: Betenbaugh
authors: Frederick J
authors: FJ
authors: Krambeck
mesh_terms: D002241:Carbohydrates / Q000032:analysis*; D045744:Cell Line, Tumor; D006031:Glycosylation; D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D011134:Polysaccharides / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000473:pathology; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D059467:Transcriptome
chemical_list: D002241:Carbohydrates; D011134:Polysaccharides