Department of Molecular Microbiology and Immunology, Keck School of Medicine, University of Southern California, CA, USA.
Department of Biostatistics and Computational Biology, University of Rochester School of Medicine and Dentistry, Rochester, NY, USA.
Bioinformatics. 2018 Jun 15;34(12):2046-2052. doi: 10.1093/bioinformatics/bty073.
Around 2.1 million new HIV-1 infections were reported in 2015, alerting that the HIV-1 epidemic remains a significant global health challenge. Precise incidence assessment strengthens epidemic monitoring efforts and guides strategy optimization for prevention programs. Estimating the onset time of HIV-1 infection can facilitate optimal clinical management and identify key populations largely responsible for epidemic spread and thereby infer HIV-1 transmission chains. Our goal is to develop a genomic assay estimating the incidence and infection time in a single cross-sectional survey setting.
We created a web-based platform, HIV-1 incidence and infection time estimator (HIITE), which processes envelope gene sequences using hierarchical clustering algorithms and informs the stage of infection, along with time since infection for incident cases. HIITE's performance was evaluated using 585 incident and 305 chronic specimens' envelope gene sequences collected from global cohorts including HIV-1 vaccine trial participants. HIITE precisely identified chronically infected individuals as being chronic with an error less than 1% and correctly classified 94% of recently infected individuals as being incident. Using a mixed-effect model, an incident specimen's time since infection was estimated from its single lineage diversity, showing 14% prediction error for time since infection. HIITE is the first algorithm to inform two key metrics from a single time point sequence sample. HIITE has the capacity for assessing not only population-level epidemic spread but also individual-level transmission events from a single survey, advancing HIV prevention and intervention programs.
Web-based HIITE and source code of HIITE are available at http://www.hayounlee.org/software.html.
Supplementary data are available at Bioinformatics online.
2015 年报告了约 210 万例新的 HIV-1 感染病例,这表明 HIV-1 疫情仍然是一个重大的全球健康挑战。准确评估发病率可加强疫情监测工作,并为预防规划的战略优化提供指导。估计 HIV-1 感染的起始时间可以促进最佳临床管理,并确定主要负责疫情传播的关键人群,从而推断 HIV-1 传播链。我们的目标是开发一种基于基因组的检测方法,用于在单次横断面研究中估计发病率和感染时间。
我们创建了一个基于网络的平台,HIV-1 发病率和感染时间估计器(HIITE),它使用层次聚类算法处理包膜基因序列,并告知感染阶段以及最近感染病例的感染后时间。使用来自包括 HIV-1 疫苗试验参与者在内的全球队列的 585 例新发和 305 例慢性标本的包膜基因序列,对 HIITE 的性能进行了评估。HIITE 精确地将慢性感染个体分类为慢性,错误率小于 1%,并正确地将 94%的新近感染个体分类为新发感染。使用混合效应模型,从单个谱系多样性估计了新发样本的感染后时间,感染后时间的预测误差为 14%。HIITE 是第一个从单个时间点序列样本中提供两个关键指标的算法。HIITE 不仅能够评估人群层面的疫情传播,还能够从单次调查中评估个体层面的传播事件,从而推进 HIV 预防和干预计划。
基于网络的 HIITE 和 HIITE 的源代码可在 http://www.hayounlee.org/software.html 上获得。
补充数据可在生物信息学在线获得。