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P311 蛋白质-蛋白质相互作用网络的重建与功能注释揭示其新功能

Reconstruction and Functional Annotation of P311 Protein-Protein Interaction Network Reveals Its New Functions.

作者信息

Wang Song, Zhang Xiaorong, Hao Fen, Li Yan, Sun Chao, Zhan Rixing, Wang Ying, He Weifeng, Li Haisheng, Luo Gaoxing

机构信息

Institute of Burn Research, State Key Laboratory of Trauma, Burn and Combined Injury, Southwest Hospital, Third Military Medical University, Chongqing, China.

Laboratory Center of Southwest Hospital, Third Military Medical University, Chongqing, China.

出版信息

Front Genet. 2019 Feb 19;10:109. doi: 10.3389/fgene.2019.00109. eCollection 2019.

Abstract

P311 is a highly conserved multifunctional protein. However, it does not belong to any established family of proteins, and its biological function has not been entirely determined. This study aims to reveal the unknown molecular and cellular function of P311. OCG (Overlapping Cluster Generator) is a clustering method used to partition a protein-protein network into overlapping clusters. Multifunctional proteins are at the intersection of relevant clusters. DAVID is an analytic tool used to extract biological meaning from a large protein list. Here we presented OD2 (OCG + DAVID + 2 human PPI datasets), a novel strategy to increase the likelihood to identify biological functions most pertinent to the multifunctional proteins. The principle of OD2 is that OCG prepares the protein lists from multifunctional protein relevant overlapping clusters, for a functional enrichment analysis by DAVID, and the similar functional enrichments, which occurs simultaneously when analyzing two human PPI datasets, are supposed to be the predicted functions. By applying OD2 to two reconstructed human PPI datasets, we supposed the function of the P311 in inflammatory responses, cell proliferation and coagulation, which were confirmed by the following biological experiments. Collectively, our study preliminarily found that P311 could play a role in inflammatory responses, cell proliferation and coagulation. Further studies are required to validate and elucidate the underlying mechanism.

摘要

P311是一种高度保守的多功能蛋白。然而,它并不属于任何已确定的蛋白家族,其生物学功能也尚未完全明确。本研究旨在揭示P311未知的分子和细胞功能。重叠簇生成器(OCG)是一种用于将蛋白质-蛋白质网络划分为重叠簇的聚类方法。多功能蛋白位于相关簇的交叉点。DAVID是一种用于从大量蛋白质列表中提取生物学意义的分析工具。在此,我们提出了OD2(OCG + DAVID + 两个人类蛋白质相互作用数据集),这是一种新策略,可提高识别与多功能蛋白最相关生物学功能的可能性。OD2的原理是,OCG从与多功能蛋白相关的重叠簇中准备蛋白质列表,以便通过DAVID进行功能富集分析,并且在分析两个人类蛋白质相互作用数据集时同时出现的相似功能富集被认为是预测功能。通过将OD2应用于两个重建的人类蛋白质相互作用数据集,我们推测了P311在炎症反应、细胞增殖和凝血中的功能,后续生物学实验证实了这些功能。总体而言,我们的研究初步发现P311可能在炎症反应、细胞增殖和凝血中发挥作用。需要进一步研究来验证和阐明其潜在机制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f7bc/6390203/c07a5b1026db/fgene-10-00109-g001.jpg

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