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DeepSIRT:一种用于鉴定 Sirtuin 靶标及其亚细胞定位的深度神经网络。

DeepSIRT: A deep neural network for identification of sirtuin targets and their subcellular localizations.

机构信息

Department of Computer Science & Engineering, Yuan Ze University, Chungli, 32003, Taiwan.

Department of Computer Science & Engineering, Yuan Ze University, Chungli, 32003, Taiwan.

出版信息

Comput Biol Chem. 2021 Aug;93:107514. doi: 10.1016/j.compbiolchem.2021.107514. Epub 2021 May 24.

Abstract

Sirtuins are a family of proteins that play a key role in regulating a wide range of cellular processes including DNA regulation, metabolism, aging/longevity, cell survival, apoptosis, and stress resistance. Sirtuins are protein deacetylases and include in the class III family of histone deacetylase enzymes (HDACs). The class III HDACs contains seven members of the sirtuin family from SIRT1 to SIRT7. The seven members of the sirtuin family have various substrates and are present in nearly all subcellular localizations including the nucleus, cytoplasm, and mitochondria. In this study, a deep neural network approach using one-dimensional Convolutional Neural Networks (CNN) was proposed to build a prediction model that can accurately identify the outcome of the sirtuin protein by targeting their subcellular localizations. Therefore, the function and localization of sirtuin targets were analyzed and annotated to compartmentalize into distinct subcellular localizations. We further reduced the sequence similarity between protein sequences and three feature extraction methods were applied in datasets. Finally, the proposed method has been tested and compared with various machine-learning algorithms. The proposed method is validated on two independent datasets and showed an average of up to 85.77 % sensitivity, 97.32 % specificity, and 0.82 MCC for seven members of the sirtuin family of proteins.

摘要

Sirtuins 是一类蛋白质,在调节多种细胞过程中发挥着关键作用,包括 DNA 调控、代谢、衰老/长寿、细胞存活、细胞凋亡和应激抵抗。Sirtuins 是蛋白质去乙酰化酶,属于组蛋白去乙酰化酶酶(HDACs)III 类。III 类 HDACs 包含从 SIRT1 到 SIRT7 的七个 Sirtuins 家族成员。Sirtuins 家族的七个成员具有不同的底物,存在于几乎所有的亚细胞定位中,包括核、细胞质和线粒体。在这项研究中,提出了一种使用一维卷积神经网络(CNN)的深度神经网络方法,以构建一个可以通过靶向其亚细胞定位来准确识别 Sirtuin 蛋白结果的预测模型。因此,对 Sirtuin 靶标的功能和定位进行了分析和注释,以将其区分为不同的亚细胞定位。我们进一步减少了蛋白质序列之间的序列相似性,并在数据集上应用了三种特征提取方法。最后,对所提出的方法进行了测试,并与各种机器学习算法进行了比较。该方法在两个独立的数据集上进行了验证,对于 Sirtuins 家族的七个成员的蛋白,平均灵敏度高达 85.77%,特异性为 97.32%,MCC 为 0.82。

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