Data_Sheet_1_Reconstruction and Functional Annotation of P311 Protein–Protein Interaction Network Reveals Its New Functions.ZIP

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.

P311是一种高度保守的多功能蛋白质，但其并不隶属于任何已确立的蛋白质家族，且其生物学功能尚未完全阐明。本研究旨在揭示P311未知的分子与细胞功能。OCG（重叠聚类生成器，Overlapping Cluster Generator）是一种可将蛋白质-蛋白质相互作用（Protein-Protein Interaction, PPI）网络划分为重叠簇的聚类方法，而多功能蛋白往往位于相关簇的交集区域。DAVID（数据库注释、可视化与整合发现工具，Database for Annotation, Visualization and Integrated Discovery）是一款用于从大规模蛋白质列表中提取生物学意义的分析工具。本研究提出了OD2（OCG + DAVID + 两个人类PPI数据集）这一全新策略，以提升鉴定与多功能蛋白最相关生物学功能的概率。OD2的核心原理为：OCG从与多功能蛋白相关的重叠簇中提取蛋白质列表，供DAVID开展功能富集分析；同时在两个人类PPI数据集的分析中均出现的相似功能富集结果，将被认定为该蛋白的预测功能。通过将OD2应用于两个重构的人类PPI数据集，我们推测P311可参与炎症反应、细胞增殖与凝血过程，该推测随后被生物学实验证实。综上，本研究初步发现P311可能在炎症反应、细胞增殖及凝血过程中发挥作用，后续仍需开展深入研究以验证该结论并阐明其潜在作用机制。