论文标题
通过统一的歧管近似和投影在HIV-1逆转录酶上识别选择的选择
Identifying Selections Operating on HIV-1 Reverse Transcriptase via Uniform Manifold Approximation and Projection
论文作者
论文摘要
我们分析了来自斯坦福大学HIV耐药性数据库的14,651个HIV1逆转录酶（HIV RT）序列，该序列用治疗方案标记，以研究该酶在该诊所的药物选择下的进化。我们的目标是确定正在进行进化的HIV RT序列空间的不同部门，以识别单个选择和/或进化解决方案。我们利用统一的歧管近似和投影（UMAP），这是一种基于图的维度降低技术，非常适合于检测非线性依赖性，并使用基于密度分析的无监督聚类算法可视化结果。我们的分析产生了21个不同的序列簇。支持这些簇的生物学意义，它们倾向于代表具有与不同治疗方案的强对应的系统发育相关的序列。因此，这种可视化艾滋病毒RT区域的方法可以帮助推断有关选择性压力的信息，尽管它是相关的。与每个集群相关的突变特征可能代表促进这些进化途径的高阶上语境，这些信息通常无法通过其他类型的突变共依赖性分析来访问。
We analyze 14,651 HIV1 reverse transcriptase (HIV RT) sequences from the Stanford HIV Drug Resistance Database labeled with treatment regimen in order to study the evolution this enzyme under drug selection in the clinic. Our goal is to identify distinct sectors of HIV RT's sequence space that are undergoing evolution as a way to identify individual selections and/or evolutionary solutions. We utilize Uniform Manifold Approximation and Projection (UMAP), a graph-based dimensionality reduction technique uniquely suited for the detection of non-linear dependencies and visualize the results using an unsupervised clustering algorithm based on density analysis. Our analysis produced 21 distinct clusters of sequences. Supporting the biological significance of these clusters, they tend to represent phylogenetically related sequences with strong correspondence to distinct treatment regimens. Thus, this method for visualization of areas of HIV RT undergoing evolution can help infer information about selective pressures, although it is correlative. The mutation signatures associated with each cluster may represent the higher-order epistatic context facilitating these evolutionary pathways, information that is generally not accessible by other types of mutational co-dependence analyses.
