PPIDomainMiner:从多种蛋白质相互作用源推断结构域-结构域相互作用。

PPIDomainMiner: Inferring domain-domain interactions from multiple sources of protein-protein interactions.

机构信息

Université de Lorraine, CNRS, Inria, LORIA, Nancy, France.

Mines Nancy, Nancy, France.

出版信息

PLoS Comput Biol. 2021 Aug 9;17(8):e1008844. doi: 10.1371/journal.pcbi.1008844. eCollection 2021 Aug.

Abstract

Many biological processes are mediated by protein-protein interactions (PPIs). Because protein domains are the building blocks of proteins, PPIs likely rely on domain-domain interactions (DDIs). Several attempts exist to infer DDIs from PPI networks but the produced datasets are heterogeneous and sometimes not accessible, while the PPI interactome data keeps growing. We describe a new computational approach called "PPIDM" (Protein-Protein Interactions Domain Miner) for inferring DDIs using multiple sources of PPIs. The approach is an extension of our previously described "CODAC" (Computational Discovery of Direct Associations using Common neighbors) method for inferring new edges in a tripartite graph. The PPIDM method has been applied to seven widely used PPI resources, using as "Gold-Standard" a set of DDIs extracted from 3D structural databases. Overall, PPIDM has produced a dataset of 84,552 non-redundant DDIs. Statistical significance (p-value) is calculated for each source of PPI and used to classify the PPIDM DDIs in Gold (9,175 DDIs), Silver (24,934 DDIs) and Bronze (50,443 DDIs) categories. Dataset comparison reveals that PPIDM has inferred from the 2017 releases of PPI sources about 46% of the DDIs present in the 2020 release of the 3did database, not counting the DDIs present in the Gold-Standard. The PPIDM dataset contains 10,229 DDIs that are consistent with more than 13,300 PPIs extracted from the IMEx database, and nearly 23,300 DDIs (27.5%) that are consistent with more than 214,000 human PPIs extracted from the STRING database. Examples of newly inferred DDIs covering more than 10 PPIs in the IMEx database are provided. Further exploitation of the PPIDM DDI reservoir includes the inventory of possible partners of a protein of interest and characterization of protein interactions at the domain level in combination with other methods. The result is publicly available at http://ppidm.loria.fr/.

摘要

许多生物过程都是由蛋白质-蛋白质相互作用(PPIs)介导的。由于蛋白质结构域是蛋白质的构建块,因此蛋白质-蛋白质相互作用可能依赖于结构域-结构域相互作用(DDIs)。已经有几种尝试从蛋白质相互作用网络中推断出 DDIs,但产生的数据集是异构的,有时不可用,而蛋白质相互作用组数据不断增长。我们描述了一种新的计算方法,称为“PPIDM”(蛋白质-蛋白质相互作用结构域挖掘器),用于使用多种蛋白质相互作用源推断 DDIs。该方法是我们之前描述的“CODAC”(使用共同邻居计算直接关联的发现)方法的扩展,用于推断三节点图中的新边。PPIDM 方法已应用于七种广泛使用的蛋白质相互作用资源,使用从 3D 结构数据库中提取的一组 DDIs 作为“黄金标准”。总体而言,PPIDM 生成了一个 84552 个非冗余 DDIs 的数据集。为每个蛋白质相互作用源计算了统计学意义(p 值),并用于将 PPIDM DDIs 分类为金(9175 个 DDIs)、银(24934 个 DDIs)和青铜(50443 个 DDIs)类别。数据集比较表明,PPIDM 从 2017 年蛋白质相互作用源的版本中推断出了 3did 数据库 2020 年版本中存在的约 46%的 DDIs,不计入黄金标准中的 DDIs。PPIDM 数据集包含 10229 个与从 IMEx 数据库中提取的超过 13300 个蛋白质相互作用一致的 DDIs,以及与从 STRING 数据库中提取的超过 214000 个人类蛋白质相互作用一致的近 23300 个 DDIs(27.5%)。提供了涵盖 IMEx 数据库中超过 10 个蛋白质相互作用的新推断 DDIs 的示例。对 PPIDM DDI 库的进一步开发包括对感兴趣蛋白质的可能伙伴的库存以及与其他方法结合在结构域级别上对蛋白质相互作用的特征描述。结果可在 http://ppidm.loria.fr/ 上公开获取。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cf3e/8376228/9d6e4f6269d0/pcbi.1008844.g001.jpg

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