A novel alignment-free method for HIV-1 subtype classification
A novel alignment-free method for HIV-1 subtype classification
复制标题
一种新的 HIV-1 亚型分类免比对方法
DOI：
10.1016/j.meegid.2019.104080
复制
发表时间：
2020-01-01
影响因子：
3.2
通讯作者：
Yau, Stephen S-T
中科院分区：
文献类型：
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作者：
He, Lily;Dong, Rui;Yau, Stephen S-T
HIV-1是人类免疫缺陷病毒中最常见的致病毒株，由许多亚型组成。为了研究不同HIV-1亚型在感染、诊断和药物设计方面的差异，从临床HIV-1样本中鉴定HIV-1亚型是很重要的。在这项工作中，我们提出了一种有效的数字表示，称为子序列自然向量（SNV）来编码HIV-1序列。在此基础上，提出了一种改进的线性判别分析方法来对HIV-1病毒进行正确的分类。SNV是基于HIV-1病毒序列中核苷酸的分布。它不仅可以计算核苷酸的数量，而且可以描述核苷酸在病毒中的位置和变异。为了验证我们的无比对方法，从最新的洛斯阿拉莫斯HIV数据库中收集了6902个完整基因组和11668个pol基因序列。SNV优于三种流行的方法，Kameris， Comet和REGA，几乎具有100%的灵敏度和特异性，而且时间也短得多。我们的亚型分型算法尤其适用于由少数序列组成的循环重组形式（CRFs）。我们的方法也能以100%的灵敏度和特异性从其他亚型中分离出独特的重组形式（urf）。此外，利用HIV-1全长基因组和pol基因分别构建了基于SNV表示的系统发育树，将相同亚型的病毒正确聚类在一起。
HIV-1 is the most common and pathogenic strain of human immunodeficiency virus consisting of many subtypes. To study the difference among HIV-1 subtypes in infection, diagnosis and drug design, it is important to identify HIV-1 subtypes from clinical HIV-1 samples. In this work, we propose an effective numeric representation called Subsequence Natural Vector (SNV) to encode HIV-1 sequences. Using the representation, we introduce an improved linear discriminant analysis method to classify HIV-1 viruses correctly. SNV is based on distribution of nucleotides in HIV-1 viral sequences. It not only computes the number of nucleotides, but also describes the position and variance of nucleotides in viruses. To validate our alignment-free method, 6902 complete genomes and 11,668 pol gene sequences of HIV-1 subtypes were collected from the up-to-date Los Alamos HIV database. SNV outperforms the three popular methods, Kameris, Comet and REGA, with almost 100% Sensitivity and Specificity, also with much less time. Our subtyping algorithm especially works better for circulating recombinant forms (CRFs) consisting of a few sequences. Our approach is also powerful to separate unique recombinant forms (URFs) from other subtypes with 100% Sensitivity and Specificity. Moreover, phylogenetic trees based on SNV representation are constructed using full-length HIV-1 genomes and pol genes respectively, where viruses from the same subtype are clustered together correctly.