Shao Jianlin, Xu Dong, Hu Landian, Kwan Yiu-Wa, Wang Yifei, Kong Xiangyin, Ngai Sai-Ming
Institute of Health Sciences, Shanghai Institutes of Biological Sciences, Chinese Academy of Sciences, Shanghai, People's Republic of China.
Mol Biosyst. 2012 Nov;8(11):2964-73. doi: 10.1039/c2mb25251a.
Lysine acetylation is a reversible post-translational modification (PTM) which has been linked to many biological and pathological implications. Hence, localization of lysine acetylation is essential for deciphering the mechanism of such implications. Whereas many acetylated lysines in human proteins have been localized through experimental approaches in wet lab, it still fails to reach completion. In the present study, we proposed a novel feature extraction approach, bi-relative adapted binomial score Bayes (BRABSB), combined with support vector machines (SVMs) to construct a human-specific lysine acetylation predictor, which yields, on average, a sensitivity of 83.91%, a specificity of 87.25% and an accuracy of 85.58%, in the case of 5-fold cross validation experiments. Results obtained through the validation on independent data sets show that the proposed approach here outperforms other existing lysine acetylation predictors. Furthermore, due to the fact that global analysis of human lysine acetylproteins, which would ultimately facilitate the systematic investigation of the biological and pathological consequences associated with lysine acetylation events, remains to be resolved, we made an attempt to systematically analyze human lysine acetylproteins, demonstrating their diversity with respect to subcellular localization as well as biological process and predominance by "binding" in terms of molecular function. Our analysis also revealed that human lysine acetylproteins are significantly enriched in neurodegenerative disorders and cancer pathways. Remarkably, lysine acetylproteins in mitochondria are significantly related to neurodegenerative disorders and those in the nucleus are instead significantly involved in pathways in cancers, all of which might ultimately provide novel global insights into such pathological processes for the therapeutic purpose. The web server is deployed at http://www.bioinfo.bio.cuhk.edu.hk/bpbphka.
赖氨酸乙酰化是一种可逆的翻译后修饰(PTM),与许多生物学和病理学意义相关。因此,赖氨酸乙酰化的定位对于解读此类意义的机制至关重要。尽管通过湿实验室的实验方法已经定位了人类蛋白质中的许多乙酰化赖氨酸,但仍未完全完成。在本研究中,我们提出了一种新颖的特征提取方法,即双相对适应二项式评分贝叶斯(BRABSB),并结合支持向量机(SVM)构建了一种人类特异性赖氨酸乙酰化预测器,在5折交叉验证实验中,其平均灵敏度为83.91%,特异性为87.25%,准确率为85.58%。通过对独立数据集的验证获得的结果表明,本文提出的方法优于其他现有的赖氨酸乙酰化预测器。此外,由于人类赖氨酸乙酰化蛋白质的全局分析仍有待解决,而这最终将有助于系统研究与赖氨酸乙酰化事件相关的生物学和病理学后果,我们尝试对人类赖氨酸乙酰化蛋白质进行系统分析,展示了它们在亚细胞定位、生物学过程方面的多样性以及在分子功能方面以“结合”为主导。我们的分析还表明,人类赖氨酸乙酰化蛋白质在神经退行性疾病和癌症途径中显著富集。值得注意的是,线粒体中的赖氨酸乙酰化蛋白质与神经退行性疾病显著相关,而细胞核中的则显著参与癌症途径,所有这些最终可能为治疗目的的此类病理过程提供新的全局见解。该网络服务器部署在http://www.bioinfo.bio.cuhk.edu.hk/bpbphka 。