iUbiq-Lys: prediction of lysine ubiquitination sites in proteins by extracting sequence evolution information via a gray system model

As one of the most important posttranslational modifications (PTMs), ubiquitination plays an important role in regulating varieties of biological processes, such as signal transduction, cell division, apoptosis, and immune response. Ubiquitination is also named “lysine ubiquitination” because it occurs when an ubiquitin is covalently attached to lysine (K) residues of targeting proteins. Given an uncharacterized protein sequence that contains many lysine residues, which one of them is the ubiquitination site, and which one is of non-ubiquitination site? With the avalanche of protein sequences generated in the postgenomic age, it is highly desired for both basic research and drug development to develop an automated method for rapidly and accurately annotating the ubiquitination sites in proteins. In view of this, a new predictor called “iUbiq-Lys” was developed based on the evolutionary information, gray system model, as well as the general form of pseudo-amino acid composition. It was demonstrated via the rigorous cross-validations that the new predictor remarkably outperformed all its counterparts. As a web-server, iUbiq-Lys is accessible to the public at http://www.jci-bioinfo.cn/iUbiq-Lys. For the convenience of most experimental scientists, we have further provided a protocol of step-by-step guide, by which users can easily get their desired results without the need to follow the complicated mathematics that were presented in this paper just for the integrity of its development process.

泛素化作为最为重要的翻译后修饰（posttranslational modifications, PTMs）之一，在调控多种生物学过程中发挥关键作用，涵盖信号转导、细胞分裂、细胞凋亡以及免疫应答等。泛素化又被称为“赖氨酸泛素化”，因为当泛素以共价键结合至靶蛋白的赖氨酸（K）残基时，即发生该修饰。给定一段包含众多赖氨酸残基的未表征蛋白质序列，如何甄别其中哪些是泛素化位点，哪些是非泛素化位点？在后基因组时代，蛋白质序列数据呈爆发式增长，因此无论是基础研究还是药物开发领域，都亟需开发一种能够快速且精准注释蛋白质泛素化位点的自动化方法。鉴于此，本研究基于进化信息、灰色系统模型以及伪氨基酸组成的通用形式，开发了一款名为“iUbiq-Lys”的预测工具。经严格的交叉验证表明，该预测工具的性能显著优于所有同类方法。作为一款在线服务器，iUbiq-Lys的公开访问地址为http://www.jci-bioinfo.cn/iUbiq-Lys。为方便多数实验科研人员使用，本研究还提供了分步操作指南，用户可借此轻松获取所需结果，无需理解本文中为保证开发过程完整性而呈现的复杂数学推导内容。