pGlycoQuant with a deep residual network for precise and minuscule-missing-value quantitative glycoproteomics enabling the functional exploration of site-specific glycosylation

Cao, W.; Kong, S.; Zeng, W.; Gong, P.; Jiang, B.; Hou, X.; Zhang, Y.; Zhao, H.; Liu, M.; Qiao, X.; Wu, M.; Yan, G.; Liu, C.; Yang, P.

doi:10.1101/2021.11.15.468561

bioRxiv · 10.1101/2021.11.15.468561

pGlycoQuant with a deep residual network for precise and minuscule-missing-value quantitative glycoproteomics enabling the functional exploration of site-specific glycosylation

Cao, W.·Kong, S.·Zeng, W.·Gong, P.·Jiang, B.·Hou, X.·Zhang, Y.·Zhao, H.·Liu, M.·Qiao, X.·Wu, M.·Yan, G.·Liu, C.·Yang, P.

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Abstract

Interpreting large-scale glycoproteomic data for intact glycopeptide identification has been tremendously advanced by software tools. However, software tools for quantitative analysis of intact glycopeptides remain lagging behind, which greatly hinders exploring the differential expression and functions of site-specific glycosylation in organisms. Here, we report pGlycoQuant, a generic software tool for accurate and convenient quantitative intact glycopeptide analysis, supporting both primary and tandem mass spectrometry quantitation for multiple quantitative strategies. pGlycoQuant enables intact glycopeptide quantitation with very low missing values via a deep residual network, thus greatly expanding the quantitative function of several powerful search engines, currently including pGlyco 2.0, pGlyco3, Byonic and MSFragger-Glyco. The pGlycoQuant-based site-specific N-glycoproteomic study conducted here quantifies 6435 intact N-glycopeptides in three hepatocellular carcinoma cell lines with different metastatic potentials and, together with in vitro molecular biology experiments, illustrates core fucosylation at site 979 of the L1 cell adhesion molecule (L1CAM) as a potential regulator of HCC metastasis. pGlycoQuant is freely available at https://github.com/expellir-arma/pGlycoQuant/releases/. We have demonstrated pGlycoQuant to be a powerful tool for the quantitative analysis of site-specific glycosylation and the exploration of potential glycosylation-related biomarker candidates, and we expect further applications in glycoproteomic studies.

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Cao, W., Kong, S., Zeng, W., Gong, P., Jiang, B., Hou, X., Zhang, Y., Zhao, H., Liu, M., Qiao, X., Wu, M., Yan, G., Liu, C., Yang, P.. 2021-11-15. pGlycoQuant with a deep residual network for precise and minuscule-missing-value quantitative glycoproteomics enabling the functional exploration of site-specific glycosylation. https://doi.org/10.1101/2021.11.15.468561

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