Revealing the Mutation Patterns of Drug-Resistant Reverse Transcriptase Variants of Human Immunodeficiency Virus through Proteochemometric Modeling.
Revealing the Mutation Patterns of Drug-Resistant Reverse Transcriptase Variants of Human Immunodeficiency Virus through Proteochemometric Modeling.
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通过蛋白化学调查模型揭示了人类免疫缺陷病毒的抗药性逆转录酶变体的突变模式。
DOI：
10.3390/biom11091302
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发表时间：
2021-09-02
期刊：
影响因子：
5.5
通讯作者：
Qiu T
中科院分区：
文献类型：
--
作者：
Qiu J;Tian X;Liu J;Qin Y;Zhu J;Xu D;Qiu T
由于逆转录酶(RT)的频繁突变，人类免疫缺陷病毒(HIV)核苷逆转录酶抑制剂(NRTI)的耐药病例不断积累。预测HIV-1NRTIs的潜在耐药性可以为临床正确使用现有药物提供指导。在这项研究中，构建了一种新的蛋白化学计量学(PCM)模型来预测六种NRTI对不同RT变异体的耐药性。用HIV-1 RT全蛋白筛选出47个显性突变位点。此后，可以推导出显性突变位点的物理化学性质以生成RT的蛋白质描述符。此外，通过结合NRTI的分子描述符，可以构建PCM模型来预测RT变体和NRTI之间的抑制能力。结果表明，该模型在外部验证集上的平均AUC值为0.946，平均精度为0.873。最后，在PCM建模的基础上，计算特征的重要性，揭示RT上的主要氨基酸分布和突变模式，反映耐药序列的特征。
Drug-resistant cases of human immunodeficiency virus (HIV) nucleoside reverse transcriptase inhibitors (NRTI) are constantly accumulating due to the frequent mutations of the reverse transcriptase (RT). Predicting the potential drug resistance of HIV-1 NRTIs could provide instructions for the proper clinical use of available drugs. In this study, a novel proteochemometric (PCM) model was constructed to predict the drug resistance between six NRTIs against different variants of RT. Forty-seven dominant mutation sites were screened using the whole protein of HIV-1 RT. Thereafter, the physicochemical properties of the dominant mutation sites can be derived to generate the protein descriptors of RT. Furthermore, by combining the molecular descriptors of NRTIs, PCM modeling can be constructed to predict the inhibition ability between RT variants and NRTIs. The results indicated that our PCM model could achieve a mean AUC value of 0.946 and a mean accuracy of 0.873 on the external validation set. Finally, based on PCM modeling, the importance of features was calculated to reveal the dominant amino acid distribution and mutation patterns on RT, to reflect the characteristics of drug-resistant sequences.
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影响因子：
4.3
作者：
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