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基于结构模型特征的两级蛋白质甲基化预测。

Two-Level Protein Methylation Prediction using structure model-based features.

机构信息

Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI, 48109, USA.

School of Mathematical Sciences and LPMC, Nankai University, Tianjin, 300071, PR China.

出版信息

Sci Rep. 2020 Apr 7;10(1):6008. doi: 10.1038/s41598-020-62883-2.

Abstract

Protein methylation plays a vital role in cell processing. Many novel methods try to predict methylation sites from protein sequence by sequence information or predicted structural information, but none of them use protein tertiary structure information in prediction. In particular, most of them do not build models for predicting methylation types (mono-, di-, tri-methylation). To address these problems, we propose a novel method, Met-predictor, to predict methylation sites and methylation types using a support vector machine-based network. Met-predictor combines a variety of sequence-based features that are derived from protein sequences with structure model-based features, which are geometric information extracted from predicted protein tertiary structure models, and are firstly used in methylation prediction. Met-predictor was tested on two independent test sets, where the addition of structure model-based features improved AUC from 0.611 and 0.520 to 0.655 and 0.566 for lysine and from 0.723 and 0.640 to 0.734 and 0.643 for arginine. When compared with other state-of-the-art methods, Met-predictor had 13.1% (3.9%) and 8.5% (16.4%) higher accuracy than the best of other methods for methyllysine and methylarginine prediction on the independent test set I (II). Furthermore, Met-predictor also attains excellent performance for predicting methylation types.

摘要

蛋白质甲基化在细胞处理中起着至关重要的作用。许多新方法试图通过序列信息或预测的结构信息从蛋白质序列中预测甲基化位点,但它们都没有在预测中使用蛋白质三级结构信息。特别是,它们中的大多数都没有建立用于预测甲基化类型(单、二、三甲基化)的模型。为了解决这些问题,我们提出了一种新的方法 Met-predictor,该方法使用基于支持向量机的网络来预测甲基化位点和甲基化类型。Met-predictor 结合了多种基于序列的特征,这些特征来自蛋白质序列,以及基于结构模型的特征,这些特征是从预测的蛋白质三级结构模型中提取的几何信息,这是首次在甲基化预测中使用。Met-predictor 在两个独立的测试集上进行了测试,其中基于结构模型的特征的加入将赖氨酸的 AUC 从 0.611 和 0.520 提高到 0.655 和 0.566,精氨酸的 AUC 从 0.723 和 0.640 提高到 0.734 和 0.643。与其他最先进的方法相比,Met-predictor 在独立测试集 I(II)上对甲基赖氨酸和甲基精氨酸的预测精度比其他方法中的最佳方法高出 13.1%(3.9%)和 8.5%(16.4%)。此外,Met-predictor 还在预测甲基化类型方面表现出了优异的性能。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dc1d/7138832/57cfb79c6200/41598_2020_62883_Fig1_HTML.jpg

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