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通过综合方法对蛋白质-蛋白质相互作用网络进行全蛋白质组范围的预测与分析。

Proteome-wide prediction and analysis of the protein-protein interaction network through integrative methods.

作者信息

Ren Panyu, Yang Xiaodi, Wang Tianpeng, Hou Yunpeng, Zhang Ziding

机构信息

State Key Laboratory of Agrobiotechnology, College of Biological Sciences, China Agricultural University, Beijing 100193, China.

出版信息

Comput Struct Biotechnol J. 2022 May 13;20:2322-2331. doi: 10.1016/j.csbj.2022.05.017. eCollection 2022.

Abstract

As one of the most studied Apicomplexan parasite () causes worldwide serious diarrhea disease cryptosporidiosis, which can be deadly to immunodeficiency individuals, newly born children, and animals. Proteome-wide identification of protein-protein interactions (PPIs) has proven valuable in the systematic understanding of the genome-phenome relationship. However, the PPIs of are largely unknown because of the limited experimental studies carried out. Therefore, we took full advantage of three bioinformatics methods, i.e., interolog mapping (IM), domain-domain interaction (DDI)-based inference, and machine learning (ML) method, to jointly predict PPIs of . Due to the lack of experimental PPIs of , we used the PPI data of (), which owned the largest number of PPIs in Apicomplexa, to train an ML model to infer PPIs. We utilized consistent results of these three methods as the predicted high-confidence PPI network, which contains 4,578 PPIs covering 554 proteins. To further explore the biological significance of the constructed PPI network, we also conducted essential network and protein functional analysis, mainly focusing on hub proteins and functional modules. We anticipate the constructed PPI network can become an important data resource to accelerate the functional genomics studies of as well as offer new hints to the target discovery in developing drugs/vaccines.

摘要

作为研究最多的顶复门寄生虫之一,(此处原文括号内容缺失)引起全球范围内严重的腹泻疾病隐孢子虫病,这对免疫缺陷个体、新生儿和动物可能是致命的。全蛋白质组范围内蛋白质 - 蛋白质相互作用(PPI)的鉴定已被证明在系统理解基因组 - 表型关系方面具有重要价值。然而,由于开展的实验研究有限,(此处原文括号内容缺失)的PPI在很大程度上尚不明确。因此,我们充分利用了三种生物信息学方法,即同源互作映射(IM)、基于结构域 - 结构域相互作用(DDI)的推断以及机器学习(ML)方法,来联合预测(此处原文括号内容缺失)的PPI。由于缺乏(此处原文括号内容缺失)的实验性PPI,我们使用了(此处原文括号内容缺失)的PPI数据(其在顶复门中拥有最多的PPI数量)来训练一个ML模型以推断(此处原文括号内容缺失)的PPI。我们将这三种方法的一致结果用作预测的高置信度PPI网络,该网络包含覆盖554个蛋白质的4578个PPI。为了进一步探索构建的PPI网络的生物学意义,我们还进行了关键网络和蛋白质功能分析,主要聚焦于枢纽蛋白和功能模块。我们预计构建的PPI网络能够成为加速(此处原文括号内容缺失)功能基因组学研究的重要数据资源,并为开发药物/疫苗中的靶点发现提供新的线索。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/de65/9120227/07654de9ca28/ga1.jpg

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