Abstract：
The aim of this study was to investigate to what extent fragments of the HEV genome could be used for accurate diagnostics and inference of viral population-scale processes. For this, we selected all the published whole genome sequences from the NCBI GenBank and trimmed them to various fragment lengths (ORF1,2,3, ORF1, ORF2, ORF3, 493 nt in ORF2 and 148 nt in ORF2). Each of the fragment lengths was used to infer the richness and diversity of the viral sequence types, typing accuracy, and potential use in phylodynamics. The results obtained from the different fragments were compared. We observed that, generally, the longer the nucleic acid fragment used in typing, the better the accuracy in predicting the viral subtype. However, the dominant HEV subtypes circulating in Europe were relatively well classified even by the 493 nt fragment, with false negative rates as low as 8 in 1000 typed sequences. Most fragments also give comparable results in analyses of population size, albeit with shorter fragments showing a broader 95 % highest posterior density interval and less obvious increase of the viral effective population size. The reconstructed phylogenies of a heterochronous subset indicated a good concordance between all the fragments, with the major clades following similar branching patterns. Furthermore, we have used the HEV sequence data from the Netherlands available in the HEVnet database as a case study for reconstruction of population size changes in the past decades. This data showed that molecular and epidemiological results are concordant and point to an increase in the viral effective population size underlying the observed increase in incidence of acute HEV infection cases. In the absence of whole genome sequencing data, the 493 bp fragment can be used for analyzing HEV strains currently circulating in Europe, as it is informative for describing short term population-scale processes.
摘要：
这项研究的目的是调查HEV基因组的片段在多大程度上可用于病毒种群规模过程的准确诊断和推断。为此，我们从NCBIGenBank中选择了所有已发布的全基因组序列，并将其修剪成各种片段长度（ORF1、2、3、ORF1、ORF2、ORF2、ORF3、ORF2中的493nt和ORF2中的148nt）。每个片段长度用于推断病毒序列类型的丰富度和多样性，打字准确性,以及在系统动力学中的潜在用途。比较从不同片段获得的结果。我们观察到,一般来说,用于分型的核酸片段越长，预测病毒亚型的准确性越好。然而,在欧洲流行的主要HEV亚型即使通过493nt片段也相对较好地分类，假阴性率低至1000个分型序列中的8个。大多数片段在人口规模分析中也给出了可比的结果，尽管较短的片段显示更广泛的95％最高后密度间隔和病毒有效种群大小的不太明显增加。非同步子集的重建系统发育表明所有片段之间具有良好的一致性，主要分支遵循类似的分支模式。此外，我们使用HEVnet数据库中提供的荷兰HEV序列数据作为重建过去几十年人口规模变化的案例研究.该数据表明，分子和流行病学结果是一致的，并指出了病毒有效种群大小的增加，这与观察到的急性HEV感染病例的发病率增加有关。在没有全基因组测序数据的情况下，493bp片段可用于分析目前在欧洲流行的HEV菌株，因为它是描述短期人口规模过程的信息。
