A strategy for precise and large scale identification of core fucosylated glycoproteins.
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 MS(3), 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.
Jia
Wei
W
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.
Lu
Zhuang
Z
Fu
Yan
Y
Wang
Hai-Peng
HP
Wang
Le-Heng
LH
Chi
Hao
H
Yuan
Zuo-Fei
ZF
Zheng
Zhao-Bin
ZB
Song
Li-Na
LN
Han
Huan-Huan
HH
Liang
Yi-Min
YM
Wang
Jing-Lan
JL
Cai
Yun
Y
Zhang
Yu-Kui
YK
Deng
Yu-Lin
YL
Ying
Wan-Tao
WT
He
Si-Min
SM
Qian
Xiao-Hong
XH
D000117:Acetylglucosamine / Q000378:metabolism; D000595:Amino Acid Sequence; D035843:Biomedical Research; D005643:Fucose / Q000378:metabolism*; D006020:Glycopeptides / Q000097:blood / Q000737:chemistry; D006023:Glycoproteins / Q000032:analysis*; D006031:Glycosylation; D006801:Humans; D013058:Mass Spectrometry; D008969:Molecular Sequence Data; D040901:Proteomics / Q000379:methods*; D014462:Ultrafiltration
D006020:Glycopeptides; D006023:Glycoproteins; D005643:Fucose; D000117:Acetylglucosamine