PROSPERous: high-throughput prediction of substrate cleavage sites for 90 proteases with improved accuracy
PROSPERous: high-throughput prediction of substrate cleavage sites for 90 proteases with improved accuracy
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DOI：
10.1093/bioinformatics/btx670
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发表时间：
2018-02-15
期刊：
影响因子：
5.8
通讯作者：
Pike, Robert N.
中科院分区：
文献类型：
--
作者：
Song, Jiangning;Li, Fuyi;Pike, Robert N.
蛋白酶是特异性切割其靶蛋白的肽骨架的酶。蛋白质切割作为一种重要的不可逆翻译后修饰，是许多重要生理过程的基础。当失调时，蛋白酶的作用与许多疾病有关。许多蛋白酶是高度特异性的，仅切割呈现某些特定氨基酸序列模式的那些靶底物。因此，成功鉴定蛋白酶的潜在靶底物的工具也可以鉴定先前未知的生理学相关切割位点，从而提供对生物过程的见解并指导旨在验证蛋白酶-底物相互作用的假设驱动的实验。在这项工作中，我们提出了PROSPERous，一种用于快速预测底物序列中蛋白酶特异性切割位点的工具。我们的工具基于逻辑回归模型，并使用不同的评分函数及其成对组合来预测潜在的切割位点。PROSPERous代表了一种最先进的工具，可以快速，准确和高通量地预测90种蛋白酶的底物切割位点。
Proteases are enzymes that specifically cleave the peptide backbone of their target proteins. As an important type of irreversible post-translational modification, protein cleavage underlies many key physiological processes. When dysregulated, proteases' actions are associated with numerous diseases. Many proteases are highly specific, cleaving only those target substrates that present certain particular amino acid sequence patterns. Therefore, tools that successfully identify potential target substrates for proteases may also identify previously unknown, physiologically relevant cleavage sites, thus providing insights into biological processes and guiding hypothesis-driven experiments aimed at verifying protease-substrate interaction. In this work, we present PROSPERous, a tool for rapid in silico prediction of protease-specific cleavage sites in substrate sequences. Our tool is based on logistic regression models and uses different scoring functions and their pairwise combinations to subsequently predict potential cleavage sites. PROSPERous represents a state-of-the-art tool that enables fast, accurate and high-throughput prediction of substrate cleavage sites for 90 proteases.