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通过整合不同类型的相互作用数据预测蛋白质复合物

Predicting protein complexes by data integration of different types of interactions.

作者信息

Tan Powell Patrick Cheng, Dargahi Daryanaz, Pio Frederic

机构信息

Molecular Biology and Biochemistry Department, Simon Fraser University, Burnaby, BC V5L 2J4, Canada.

出版信息

Int J Comput Biol Drug Des. 2010;3(1):19-30. doi: 10.1504/IJCBDD.2010.034464. Epub 2010 Aug 5.

Abstract

The explosion of high throughput interaction data from proteomics studies gives us the opportunity to integrate Protein-Protein Interactions (PPI) from different type of interactions. These methods rely on the assumption that proteins within a complex have more interactions across the different data sets which translate into the identification of dense subgraphs. However, the relative importance of the types of interaction are not equivalent in their reliability and accuracy consequently they should be analysed separately. Here we propose a method that use graph theory and mathematical modelling to solve this problem. Our approach has four steps that: i) score independently each type of interaction; ii) build an interaction specific networks for each type; iii) weight the specific networks; and iv) combine and normalise the scores. Using this approach to the BRCA1 Associated genome Surveillance Complex (BASC), we correctly identified the known core components of the complex and subcomplexes that have solved structures as well as predicted new interactions and core complexes. The method presented in this study is of general use. It is flexible enough to allow the development of any scoring system and can be applied to any protein complex to provide the latest knowledge in its interactions and structure.

摘要

蛋白质组学研究中高通量相互作用数据的激增,让我们有机会整合来自不同类型相互作用的蛋白质-蛋白质相互作用(PPI)。这些方法基于这样一种假设:复合物中的蛋白质在不同数据集中有更多相互作用,这转化为对密集子图的识别。然而,不同类型相互作用的相对重要性在可靠性和准确性方面并不等同,因此应分别进行分析。在此,我们提出一种利用图论和数学建模来解决此问题的方法。我们的方法有四个步骤:i)独立对每种相互作用类型进行评分;ii)为每种类型构建特定于相互作用的网络;iii)对特定网络进行加权;iv)合并并归一化分数。将这种方法应用于乳腺癌1号基因相关基因组监测复合物(BASC),我们正确识别出了该复合物及已解析结构的亚复合物的已知核心成分,同时预测了新的相互作用和核心复合物。本研究中提出的方法具有普遍适用性。它足够灵活,能够开发任何评分系统,并可应用于任何蛋白质复合物,以提供其相互作用和结构方面的最新知识。

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