A top-down approach to infer and compare domain-domain interactions across eight model organisms.
A top-down approach to infer and compare domain-domain interactions across eight model organisms.
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DOI：
10.1371/journal.pone.0005096
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发表时间：
2009
期刊：
影响因子：
3.7
通讯作者：
Guda P
中科院分区：
文献类型：
--
作者：
Guda C;King BR;Pal LR;Guda P
特定结构域-结构域相互作用（DDI）的知识对于理解蛋白质相互作用网络的功能意义至关重要。尽管有大量关于蛋白质-蛋白质相互作用（PPI）的数据，但对其中发生的特定DDI知之甚少。在这里，我们提出了一个自上而下的方法来准确地推断PPI数据的功能相关的DDI。我们通过结合来自五个主要交互数据库的数据集，创建了一个由209，165个实验衍生的PPI组成的全面的非冗余数据集。我们介绍了一个集成的评分系统，它使用一组五个正交评分功能的新组合，涵盖了概率，进化，循证，空间和功能特性的相互作用域，它可以映射在许多方面的两个域的相互作用倾向。该方法在预测精度和域交互空间覆盖率方面均优于现有的同类方法。我们预测了一组52，492个高置信度的DDI，对包括人、小鼠、果蝇、C.秀丽隐杆线虫、酵母菌、疟原虫、E. coli和拟南芥属。我们的研究结果表明，只有23%的这些DDI是保守的，在至少两个物种，只有3.8%，在至少4个物种，表明一个相当低的物种之间的保守性。DDI保护的成对分析揭示了进化上相邻物种之间的“滑动保护”模式。我们的方法和本研究中产生的高置信度DDI预测可以帮助更好地理解PPI在模块水平上的功能意义，从而可以显着影响系统生物学研究中的进一步实验研究。
Knowledge of specific domain-domain interactions (DDIs) is essential to understand the functional significance of protein interaction networks. Despite the availability of an enormous amount of data on protein-protein interactions (PPIs), very little is known about specific DDIs occurring in them. Here, we present a top-down approach to accurately infer functionally relevant DDIs from PPI data. We created a comprehensive, non-redundant dataset of 209,165 experimentally-derived PPIs by combining datasets from five major interaction databases. We introduced an integrated scoring system that uses a novel combination of a set of five orthogonal scoring features covering the probabilistic, evolutionary, evidence-based, spatial and functional properties of interacting domains, which can map the interacting propensity of two domains in many dimensions. This method outperforms similar existing methods both in the accuracy of prediction and in the coverage of domain interaction space. We predicted a set of 52,492 high-confidence DDIs to carry out cross-species comparison of DDI conservation in eight model species including human, mouse, Drosophila, C. elegans, yeast, Plasmodium, E. coli and Arabidopsis. Our results show that only 23% of these DDIs are conserved in at least two species and only 3.8% in at least 4 species, indicating a rather low conservation across species. Pair-wise analysis of DDI conservation revealed a ‘sliding conservation’ pattern between the evolutionarily neighboring species. Our methodology and the high-confidence DDI predictions generated in this study can help to better understand the functional significance of PPIs at the modular level, thus can significantly impact further experimental investigations in systems biology research.
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