Department of Bioinformatics and Systems Biology, Key Laboratory of Molecular Biophysics of the Ministry of Education, Hubei Bioinformatics and Molecular Imaging Key Laboratory, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan 430074, China.
School of Life Sciences, Zhengzhou University, Zhengzhou 450001, China.
Genomics Proteomics Bioinformatics. 2020 Apr;18(2):194-207. doi: 10.1016/j.gpb.2019.11.010. Epub 2020 Aug 28.
As an important protein acylation modification, lysine succinylation (Ksucc) is involved in diverse biological processes, and participates in human tumorigenesis. Here, we collected 26,243 non-redundant known Ksucc sites from 13 species as the benchmark data set, combined 10 types of informative features, and implemented a hybrid-learning architecture by integrating deep-learning and conventional machine-learning algorithms into a single framework. We constructed a new tool named HybridSucc, which achieved area under curve (AUC) values of 0.885 and 0.952 for general and human-specific prediction of Ksucc sites, respectively. In comparison, the accuracy of HybridSucc was 17.84%-50.62% better than that of other existing tools. Using HybridSucc, we conducted a proteome-wide prediction and prioritized 370 cancer mutations that change Ksucc states of 218 important proteins, including PKM2, SHMT2, and IDH2. We not only developed a high-profile tool for predicting Ksucc sites, but also generated useful candidates for further experimental consideration. The online service of HybridSucc can be freely accessed for academic research at http://hybridsucc.biocuckoo.org/.
赖氨酸琥珀酰化(Ksucc)作为一种重要的蛋白质酰化修饰,参与多种生物学过程,并参与人类肿瘤发生。在这里,我们收集了来自 13 个物种的 26,243 个非冗余已知 Ksucc 位点作为基准数据集,结合了 10 种信息特征,并通过将深度学习和传统机器学习算法集成到单个框架中,实现了混合学习架构。我们构建了一个名为 HybridSucc 的新工具,它分别实现了 0.885 和 0.952 的曲线下面积 (AUC) 值,用于一般和人类特异性 Ksucc 位点的预测。相比之下,HybridSucc 的准确性比其他现有工具高 17.84%-50.62%。使用 HybridSucc,我们进行了全蛋白质组预测,并优先考虑了 370 种癌症突变,这些突变改变了 218 种重要蛋白质的 Ksucc 状态,包括 PKM2、SHMT2 和 IDH2。我们不仅开发了一种用于预测 Ksucc 位点的高性能工具,还为进一步的实验考虑生成了有用的候选物。HybridSucc 的在线服务可在 http://hybridsucc.biocuckoo.org/ 上免费供学术研究使用。