Genome-wide classification and identification of transmembrane protein structure and function

我们首先从文献中收集实验表征的跨膜拓扑模型，并将它们构建到数据库(TMBDB)中。在此基础上，我们对已发表的几种跨膜拓扑预测方法的性能进行了评估，并提出了一种结合这些方法的一致性预测方法(ConPred)。通过对99个完整的基因组(88个原核生物和12个真核生物)的TM蛋白质组进行ConPred分析，我们获得了52,686个具有可靠TM拓扑结构的TM蛋白质序列，并详细分析了它们的TM拓扑结构与功能的关系。分析表明，TM蛋白的功能与其TM拓扑结构密切相关，并且每个功能基团pfTM蛋白都有自己独特的TM拓扑模式，表现为二元拓扑模式。应用二元拓扑图谱方法对gpcr基因进行了基因组级功能分类和鉴定，发现了许多新的gpcr基因。我们还通过单序列内的内部序列相似性比较，研究了基因内部复制对TM拓扑进化的影响。

We first collected experimentally-characterized transmembrane topology models from literatures and constructed them into a database(TMBDB). By using this, we evaluated the performances of several published transmembrane topology prediction methods, and we developed a consensus prediction method(ConPred) which is a combination of some of the proposed methods. By applying ConPred to TM proteomes from 99 completed genomes(88 prokaryotic and 12 eukaryotic), we obtained 52,686 TM protein sequences with reliable TM topologies and analysed the TM topologies of them in detail with respect to their relation to the function. From this analysis, it was revealed that the function of TM protein is closely related to its TM topology, and each functional group pfTM proteins has its own specific TM topology pattern expressed as a binary topology patter. The genome-scale functional classification and identification of GPCRs were also earned out, by applying the binary topology pattern method, and many novel GPCR genes were found by our study. We also investigated die TM topology evolution by internal gene duplication, through the internal sequence similarity comparison within a single sequences.