SCOTCH: subtype A coreceptor tropism classification in HIV-1
SCOTCH: subtype A coreceptor tropism classification in HIV-1
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DOI：
10.1093/bioinformatics/bty170
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发表时间：
2018-08-01
期刊：
影响因子：
5.8
通讯作者：
Heider, Dominik
中科院分区：
文献类型：
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作者：
Loechel, Hannah F.;Riemenschneider, Mona;Heider, Dominik
动机：人类免疫缺陷病毒1型(HIV-1)gp120糖蛋白的V3环被认为是病毒协同受体趋向性的原因。Gp120与宿主细胞的CD4受体相互作用，随后V3与CCR5或CXCR4结合。由于CCR5辅助受体是进入抑制剂的靶点，可靠地预测HIV-1的辅助受体的使用对抗逆转录病毒治疗非常有意义。虽然有几种预测辅受体趋向性的方法，但几乎所有的方法都是基于B亚型序列开发的，而且一些研究表明，对非B序列，特别是A亚型序列的预测不那么可靠。因此，本研究的目的是开发一种可靠的A亚型病毒预测模型。结果：我们的新模型Scotch基于分类器集成的堆叠方法，与其他现有模型相比，对A亚型序列的预测性能明显更好。特别是对于较低的假阳性率(在0.05和0.2之间，即德国和欧洲关于趋向性预测的指南中的建议)，Scotch在曲线下的部分面积和诊断优势比方面表现出比现有工具显著更好的预测性能，因此可以用于可靠地预测A亚型序列的辅受体趋向性。
Motivation: The V3 loop of the gp120 glycoprotein of the Human Immunodeficiency Virus 1 (HIV-1) is considered to be responsible for viral coreceptor tropism. gp120 interacts with the CD4 receptor of the host cell and subsequently V3 binds either CCR5 or CXCR4. Due to the fact that the CCR5 coreceptor is targeted by entry inhibitors, a reliable prediction of the coreceptor usage of HIV-1 is of great interest for antiretroviral therapy. Although several methods for the prediction of coreceptor tropism are available, almost all of them have been developed based on only subtype B sequences, and it has been shown in several studies that the prediction of non-B sequences, in particular subtype A sequences, are less reliable. Thus, the aim of the current study was to develop a reliable prediction model for subtype A viruses.Results: Our new model SCOTCH is based on a stacking approach of classifier ensembles and shows a significantly better performance for subtype A sequences compared to other available models. In particular for low false positive rates (between 0.05 and 0.2, i.e. recommendation in the German and European Guidelines for tropism prediction), SCOTCH shows significantly better prediction performances in terms of partial area under the curves and diagnostic odds ratios compared to existing tools, and thus can be used to reliably predict coreceptor tropism for subtype A sequences.