The Virus Analysis Tool (VAT) - A computational tool for the characterisation and monitoring of viruses during an acute outbreak

对新病毒爆发的反应的一个主要限制是缺乏信息。虽然下一代测序鉴定病毒的速度很快，但对病毒临床和生物学特性的调查需要更长的时间。此外，需要早期检测病原性、传播性、药物敏感性和/或免疫原性发生变化的新病毒株。计算方法有可能填补这些空白。我们创造了一种方法，通过识别相关病毒之间不同保守的氨基酸序列位置，并随后对其对蛋白质结构/功能的影响进行计算建模，来识别病毒行为的决定因素。我们的研究已经确定了SARS-CoV-2和SARS-CoV之间的实质性差异。虽然SARS-CoV-2和SARS-CoV的序列同源性约为80%，但其余大部分位置是差异保守的，这反映在临床行为、细胞嗜性和药物敏感性上的差异。在这里，我们将把这种方法发展成一个网络服务器(‘病毒分析工具’，VAT)，可以被参与SARS-CoV-2研究和治疗的每个人使用。在目前的疫情中，增值税将使研究人员能够将新的SARS-CoV-2毒株的基因组序列与其他SARS-CoV-2毒株的基因组序列进行比较，并快速识别新的毒株，这些毒株的特征可能是表型的变化，例如疾病严重程度、药物敏感性或免疫原性。因此，增值税将成为有效监测新病毒变种出现的工具。增值税还将加强我们对未来病毒爆发的准备。

A main limitation of the response to novel virus outbreaks is the lack of information. While virus identification by next generation sequencing is quick, the investigation of the clinical and biological virus properties takes much longer. Moreover, methods for the early detection of novel virus strains with changed pathogenicity, transmissibility, drug sensitivity, and/ or immunogenicity are needed. Computational approaches have the potential to fill these gaps. We have created a method that identifies determinants of virus behaviour by identifying amino acid sequence positions that are differently conserved between related viruses and subsequent computational modelling of their impact on protein structure/ function. Our research has already identified substantial differences between SARS-CoV-2 and SARS-CoV. Although SARS-CoV-2 and SARS-CoV share a sequence identity of about 80%, the majority of the remaining positions are differentially conserved, which is reflected in differences in clinical behaviour, cell tropism, and drug sensitivity. Here, we will develop this approach into a webserver (the 'Virus Analysis Tool', VAT) that can be used by everyone involved in SARS-CoV-2 research and treatment. In the current outbreak, VAT will enable researchers to compare the genomic sequences of novel SARS-CoV-2 isolates to those of other SARS-CoV-2 strains and to identify novel strains rapidly, which are likely to be characterised by changes in phenotype, for example in disease severity, drug sensitivity, or immunogenicity. Hence, VAT will be a tool for the effective monitoring of the emergence of novel virus variants. VAT will also increase our preparedness for future virus outbreaks.