How and when should interactome-derived clusters be used to predict functional modules and protein function?

How and when should interactome-derived clusters be used to predict functional modules and protein function?
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DOI:
10.1093/bioinformatics/btp551
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发表时间:
2009-12-01
期刊:
Bioinformatics (Oxford, England)
影响因子:
--
通讯作者:
Singh M
Singh M
中科院分区:
其他
文献类型:
--
作者:
Song J;Singh M

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动机:蛋白质相互作用网络的聚类是预测蛋白质功能模块、蛋白质复合物和蛋白质功能的最常用方法之一。但是,集群在这些任务中的表现如何?结果如下:我们开发了一个通用的框架,以评估如何以及计算得出的集群在物理相互作用重叠的功能模块通过基因本体论(GO)。使用这个框架,我们评估六种不同的网络聚类算法,使用酿酒酵母,并表明(i)这些算法的性能可以有很大的不同,当运行在同一个网络和(ii)它们的相对性能的变化取决于所考虑的网络的拓扑特征。对于酿酒酵母中的功能预测的特定任务,我们证明,令人惊讶的是,一个简单的非聚类内疚的关联方法优于广泛使用的基于聚类的方法,注释蛋白质与过度代表的生物过程和细胞成分的条款在其集群,这是真的聚类算法的范围内考虑。进一步的分析参数化的基础上的注释蛋白质的数量的性能,并建议聚类方法应用于相互作用组功能分析。总的来说,我们的研究结果表明,重新检查何时以及如何聚类方法应适用于物理interactomes,并建立新的聚类方法生物网络的指导方针,应合理和评估功能分析。联系方式:msingh@cs.princeton.edu补充信息:补充数据可从生物信息学在线网站获得。
Motivation: Clustering of protein–protein interaction networks is one of the most common approaches for predicting functional modules, protein complexes and protein functions. But, how well does clustering perform at these tasks? Results: We develop a general framework to assess how well computationally derived clusters in physical interactomes overlap functional modules derived via the Gene Ontology (GO). Using this framework, we evaluate six diverse network clustering algorithms using Saccharomyces cerevisiae and show that (i) the performances of these algorithms can differ substantially when run on the same network and (ii) their relative performances change depending upon the topological characteristics of the network under consideration. For the specific task of function prediction in S.cerevisiae, we demonstrate that, surprisingly, a simple non-clustering guilt-by-association approach outperforms widely used clustering-based approaches that annotate a protein with the overrepresented biological process and cellular component terms in its cluster; this is true over the range of clustering algorithms considered. Further analysis parameterizes performance based on the number of annotated proteins, and suggests when clustering approaches should be used for interactome functional analyses. Overall our results suggest a re-examination of when and how clustering approaches should be applied to physical interactomes, and establishes guidelines by which novel clustering approaches for biological networks should be justified and evaluated with respect to functional analysis. Contact: msingh@cs.princeton.edu Supplementary information: Supplementary data are available at Bioinformatics online.
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