Annotating activation/inhibition relationships to protein-protein interactions using gene ontology relations.

Annotating activation/inhibition relationships to protein-protein interactions using gene ontology relations.
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DOI:
10.1186/s12918-018-0535-4
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发表时间:
2018-04-11
影响因子:
--
通讯作者:
Lee D
Lee D
中科院分区:
生物2区
文献类型:
--
作者:
Yim S;Yu H;Jang D;Lee D

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信号通路可以通过识别蛋白质-蛋白质相互作用(PPI)的“效应类型”(即激活/抑制)来重建。效应类型由“方向”(即上游/下游)和“符号”(即正/负)组成,因此需要 PPI 的方向和符号来预测来自 PPI 网络的信号事件。在这里,我们提出了一种利用蛋白质功能信息之间的关系系统地注释 PPI 效应类型的计算方法。我们利用基因本体论(GO)中的调节、正调节和负调节关系来预测 PPI 的方向和迹象。这些关系表明了 GO 项之间的方向和符号,以便我们可以将相关 GO 项之间的方向和符号投影到 PPI。独立测试结果表明,我们的方法对于预测 PPI 的方向和迹象是有效的。此外,我们的方法优于之前基于 GO 的方法,该方法没有考虑 GO 术语之间的关系。我们注释了人类 PPI 的效应类型,并根据文献验证了几种高度可信的效应类型。带注释的人类 PPI 可在附加文件 2 中找到,以帮助信号通路重建和网络生物学研究。我们通过使用 GO 中的调节、正向调节和负向调节关系来注释 PPI 的效应类型。我们证明,这些关系不仅可以有效预测 PPI 的迹象,还可以有效预测 PPI 的方向。这些关系的有用性表明它们在其他类型的相互作用(例如蛋白质-DNA 相互作用)中的潜在应用。本文的在线版本 (10.1186/s12918-018-0535-4) 包含补充材料,可供授权用户使用。
Signaling pathways can be reconstructed by identifying ‘effect types’ (i.e. activation/inhibition) of protein-protein interactions (PPIs). Effect types are composed of ‘directions’ (i.e. upstream/downstream) and ‘signs’ (i.e. positive/negative), thereby requiring directions as well as signs of PPIs to predict signaling events from PPI networks. Here, we propose a computational method for systemically annotating effect types to PPIs using relations between functional information of proteins. We used regulates, positively regulates, and negatively regulates relations in Gene Ontology (GO) to predict directions and signs of PPIs. These relations indicate both directions and signs between GO terms so that we can project directions and signs between relevant GO terms to PPIs. Independent test results showed that our method is effective for predicting both directions and signs of PPIs. Moreover, our method outperformed a previous GO-based method that did not consider the relations between GO terms. We annotated effect types to human PPIs and validated several highly confident effect types against literature. The annotated human PPIs are available in Additional file 2 to aid signaling pathway reconstruction and network biology research. We annotated effect types to PPIs by using regulates, positively regulates, and negatively regulates relations in GO. We demonstrated that those relations are effective for predicting not only signs, but also directions of PPIs. The usefulness of those relations suggests their potential applications to other types of interactions such as protein-DNA interactions. The online version of this article (10.1186/s12918-018-0535-4) contains supplementary material, which is available to authorized users.
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