Department of Physiology and Neurobiology, University of Connecticut, Storrs, CT 06269-3156, U.S.A.
Essays Biochem. 2012;52:165-77. doi: 10.1042/bse0520165.
Our understanding of the importance of lysine post-translational modifications in mediating protein function has led to a significant improvement in the experimental tools aimed at characterizing their existence. Nevertheless, it remains likely that at present we have only experimentally detected a small fraction of all lysine modification sites across the commonly studied proteomes. As a result, online computational tools aimed at predicting lysine modification sites have the potential to provide valuable insight to researchers developing hypotheses regarding these modifications. This chapter discusses the metrics and procedures used to assess predictive tools and surveys 11 online computational tools aimed at the prediction of the four most widely studied lysine post-translational modifications (acetylation, methylation, SUMOylation and ubiquitination). Analyses using unbiased testing data sets suggest that nine of the 11 lysine post-translational modification tools perform no better than random, or have false-positive rates which make them unusable by the experimental biologist, despite self-reported sensitivity and specificity values to the contrary. The implications of these findings for those using and creating lysine post-translational modification software are discussed.
我们对赖氨酸翻译后修饰在介导蛋白质功能中的重要性的理解，导致了用于描述其存在的实验工具的显著改进。然而，目前很可能我们仅通过实验检测到了在常见研究的蛋白质组中所有赖氨酸修饰位点的一小部分。因此，旨在预测赖氨酸修饰位点的在线计算工具有可能为研究人员提供关于这些修饰的假设开发提供有价值的见解。本章讨论了用于评估预测工具的指标和程序，并调查了 11 种旨在预测四种最广泛研究的赖氨酸翻译后修饰（乙酰化、甲基化、SUMO 化和泛素化）的在线计算工具。使用无偏测试数据集的分析表明，11 种赖氨酸翻译后修饰工具中的 9 种表现并不优于随机，或者具有假阳性率，使得它们对实验生物学家来说无法使用，尽管它们报告了相反的敏感性和特异性值。这些发现对使用和创建赖氨酸翻译后修饰软件的人的影响进行了讨论。
