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Molecular & Cellular Proteomics 8:913-923, 2009.
© 2009 by The American Society for Biochemistry and Molecular Biology, Inc.

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Research

A Strategy for Precise and Large Scale Identification of Core Fucosylated Glycoproteins^*,S

Wei Jia^,,¶, Zhuang Lu^,¶,||, Yan Fu^¶,**, Hai-Peng Wang^**, Le-Heng Wang^**, Hao Chi^**, Zuo-Fei Yuan^**, Zhao-Bin Zheng, Li-Na Song, Huan-Huan Han, Yi-Min Liang, Jing-Lan Wang, Yun Cai, Yu-Kui Zhang^||, Yu-Lin Deng^||, Wan-Tao Ying^,, Si-Min He^**, and Xiao-Hong Qian^,¶¶

From the State Key Laboratory of Proteomics-Beijing Proteome Research Center-Beijing Institute of Radiation Medicine, No. 33 Life Science Park Road, Changping District, Beijing 102206, China, Institute of Biophysics, Chinese Academy of Sciences, No. 15 Datun Road, Chaoyang District, Beijing 100101, China, ^|| Beijing Institute of Technology, No. 5 South Zhongguancun Street, Haidian District, Beijing 100081, China, and ^** Institute of Computing Technology, Chinese Academy of Sciences, No. 6 Kexueyuan South Road, Beijing 100190, China

Core fucosylation (CF) patterns of some glycoproteins are more sensitive and specific than evaluation of their total respective protein levels for diagnosis of many diseases, such as cancers. Global profiling and quantitative characterization of CF glycoproteins may reveal potent biomarkers for clinical applications. However, current techniques are unable to reveal CF glycoproteins precisely on a large scale. Here we developed a robust strategy that integrates molecular weight cutoff, neutral loss-dependent MS³, database-independent candidate spectrum filtering, and optimization to effectively identify CF glycoproteins. The rationale for spectrum treatment was innovatively based on computation of the mass distribution in spectra of CF glycopeptides. The efficacy of this strategy was demonstrated by implementation for plasma from healthy subjects and subjects with hepatocellular carcinoma. Over 100 CF glycoproteins and CF sites were identified, and over 10,000 mass spectra of CF glycopeptide were found. The scale of identification results indicates great progress for finding biomarkers with a particular and attractive prospect, and the candidate spectra will be a useful resource for the improvement of database searching methods for glycopeptides.

To whom correspondence may be addressed. E-mail: smhe{at}ict.ac.cn

^¶¶ To whom correspondence may be addressed. E-mail: qianxh1{at}yahoo.com.cn

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