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Quokka:一种全面的工具,可快速准确地预测人类蛋白质组中激酶家族特异性磷酸化位点。

Quokka: a comprehensive tool for rapid and accurate prediction of kinase family-specific phosphorylation sites in the human proteome.

机构信息

Biomedicine Discovery Institute and Department of Biochemistry and Molecular Biology, Monash University, Clayton, VIC, Australia.

Department of Biology, Institute of Molecular Systems Biology, ETH Zurich, Zurich, Switzerland.

出版信息

Bioinformatics. 2018 Dec 15;34(24):4223-4231. doi: 10.1093/bioinformatics/bty522.

Abstract

MOTIVATION

Kinase-regulated phosphorylation is a ubiquitous type of post-translational modification (PTM) in both eukaryotic and prokaryotic cells. Phosphorylation plays fundamental roles in many signalling pathways and biological processes, such as protein degradation and protein-protein interactions. Experimental studies have revealed that signalling defects caused by aberrant phosphorylation are highly associated with a variety of human diseases, especially cancers. In light of this, a number of computational methods aiming to accurately predict protein kinase family-specific or kinase-specific phosphorylation sites have been established, thereby facilitating phosphoproteomic data analysis.

RESULTS

In this work, we present Quokka, a novel bioinformatics tool that allows users to rapidly and accurately identify human kinase family-regulated phosphorylation sites. Quokka was developed by using a variety of sequence scoring functions combined with an optimized logistic regression algorithm. We evaluated Quokka based on well-prepared up-to-date benchmark and independent test datasets, curated from the Phospho.ELM and UniProt databases, respectively. The independent test demonstrates that Quokka improves the prediction performance compared with state-of-the-art computational tools for phosphorylation prediction. In summary, our tool provides users with high-quality predicted human phosphorylation sites for hypothesis generation and biological validation.

AVAILABILITY AND IMPLEMENTATION

The Quokka webserver and datasets are freely available at http://quokka.erc.monash.edu/.

SUPPLEMENTARY INFORMATION

Supplementary data are available at Bioinformatics online.

摘要

动机

激酶调节的磷酸化是真核和原核细胞中普遍存在的一种翻译后修饰(PTM)类型。磷酸化在许多信号通路和生物过程中发挥着基本作用,如蛋白质降解和蛋白质-蛋白质相互作用。实验研究表明,异常磷酸化引起的信号缺陷与多种人类疾病,尤其是癌症密切相关。有鉴于此,已经建立了许多旨在准确预测蛋白激酶家族特异性或激酶特异性磷酸化位点的计算方法,从而促进了磷酸蛋白质组学数据分析。

结果

在这项工作中,我们提出了 Quokka,这是一种新的生物信息学工具,允许用户快速准确地识别人类激酶家族调节的磷酸化位点。Quokka 的开发使用了多种序列评分函数,并结合了优化的逻辑回归算法。我们基于精心准备的最新基准和独立测试数据集对 Quokka 进行了评估,这些数据集分别来自 Phospho.ELM 和 UniProt 数据库。独立测试表明,与用于磷酸化预测的最先进的计算工具相比,Quokka 提高了预测性能。总之,我们的工具为假设生成和生物学验证提供了高质量的预测人类磷酸化位点。

可用性和实现

Quokka 网络服务器和数据集可在 http://quokka.erc.monash.edu/ 免费获得。

补充信息

补充数据可在生物信息学在线获得。

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