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解读HIV耐药性:从基因型到治疗

Decoding HIV resistance: from genotype to therapy.

作者信息

Weber Irene T, Harrison Robert W

机构信息

Department of Biology, Georgia State University, PO Box 4010, Atlanta, GA 30302-4010, USA.

Department of Computer Science, Georgia State University, Atlanta, GA 30303, USA.

出版信息

Future Med Chem. 2017 Sep;9(13):1529-1538. doi: 10.4155/fmc-2017-0048. Epub 2017 Aug 9.

Abstract

Genetic variation in HIV poses a major challenge for prevention and treatment of the AIDS pandemic. Resistance occurs by mutations in the target proteins that lower affinity for the drug or alter the protein dynamics, thereby enabling viral replication in the presence of the drug. Due to the prevalence of drug-resistant strains, monitoring the genotype of the infecting virus is recommended. Computational approaches for predicting resistance from genotype data and guiding therapy are discussed. Many prediction methods rely on rules derived from known resistance-associated mutations, however, statistical or machine learning can improve the classification accuracy and assess unknown mutations. Adding classifiers such as information on the atomic structure of the protein can further enhance the predictions.

摘要

人类免疫缺陷病毒(HIV)的基因变异给艾滋病大流行的预防和治疗带来了重大挑战。耐药性是由靶蛋白中的突变引起的,这些突变会降低对药物的亲和力或改变蛋白质动力学,从而使病毒在有药物存在的情况下仍能复制。由于耐药菌株的普遍存在,建议监测感染病毒的基因型。本文讨论了从基因型数据预测耐药性并指导治疗的计算方法。许多预测方法依赖于从已知的耐药相关突变中得出的规则,然而,统计或机器学习可以提高分类准确性并评估未知突变。添加诸如蛋白质原子结构信息等分类器可以进一步提高预测效果。

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