Sun Jingchun, Sun Yan, Ding Guohui, Liu Qi, Wang Chuan, He Youyu, Shi Tieliu, Li Yixue, Zhao Zhongming
Virginia Institute for Psychiatric and Behavioral Genetics and Department of Psychiatry, Virginia Commonwealth University, Richmond, VA 23298, USA.
BMC Bioinformatics. 2007 Oct 26;8:414. doi: 10.1186/1471-2105-8-414.
Although many genomic features have been used in the prediction of protein-protein interactions (PPIs), frequently only one is used in a computational method. After realizing the limited power in the prediction using only one genomic feature, investigators are now moving toward integration. So far, there have been few integration studies for PPI prediction; one failed to yield appreciable improvement of prediction and the others did not conduct performance comparison. It remains unclear whether an integration of multiple genomic features can improve the PPI prediction and, if it can, how to integrate these features.
In this study, we first performed a systematic evaluation on the PPI prediction in Escherichia coli (E. coli) by four genomic context based methods: the phylogenetic profile method, the gene cluster method, the gene fusion method, and the gene neighbor method. The number of predicted PPIs and the average degree in the predicted PPI networks varied greatly among the four methods. Further, no method outperformed the others when we tested using three well-defined positive datasets from the KEGG, EcoCyc, and DIP databases. Based on these comparisons, we developed a novel integrated method, named InPrePPI. InPrePPI first normalizes the AC value (an integrated value of the accuracy and coverage) of each method using three positive datasets, then calculates a weight for each method, and finally uses the weight to calculate an integrated score for each protein pair predicted by the four genomic context based methods. We demonstrate that InPrePPI outperforms each of the four individual methods and, in general, the other two existing integrated methods: the joint observation method and the integrated prediction method in STRING. These four methods and InPrePPI are implemented in a user-friendly web interface.
This study evaluated the PPI prediction by four genomic context based methods, and presents an integrated evaluation method that shows better performance in E. coli.
尽管许多基因组特征已被用于预测蛋白质-蛋白质相互作用(PPI),但在计算方法中通常仅使用一种。在意识到仅使用一种基因组特征进行预测的能力有限之后,研究人员现在正朝着整合的方向发展。到目前为止,针对PPI预测的整合研究很少;一项研究未能在预测方面取得明显改进,其他研究则未进行性能比较。目前尚不清楚整合多种基因组特征是否能改善PPI预测,如果可以,如何整合这些特征。
在本研究中,我们首先通过四种基于基因组背景的方法对大肠杆菌中的PPI预测进行了系统评估:系统发育谱方法、基因簇方法、基因融合方法和基因邻域方法。这四种方法预测的PPI数量以及预测的PPI网络中的平均度数差异很大。此外,当我们使用来自KEGG、EcoCyc和DIP数据库的三个定义明确的阳性数据集进行测试时,没有一种方法优于其他方法。基于这些比较,我们开发了一种新的整合方法,名为InPrePPI。InPrePPI首先使用三个阳性数据集对每种方法的AC值(准确性和覆盖率的综合值)进行归一化,然后计算每种方法的权重,最后使用权重为基于四种基因组背景的方法预测的每个蛋白质对计算综合得分。我们证明InPrePPI优于四种单独方法中的每一种,并且总体上优于其他两种现有的整合方法:联合观察法和STRING中的整合预测法。这四种方法和InPrePPI都在一个用户友好的网络界面中实现。
本研究评估了四种基于基因组背景的方法对PPI的预测,并提出了一种在大肠杆菌中表现更好的整合评估方法。