Al Khalaf Ruba, Bernasconi Anna, Pinoli Pietro, Ceri Stefano
Dipartimento di Elettronica, Informazione e Bioingegneria, Politecnico di Milano, Milan, Italy.
Comput Struct Biotechnol J. 2022;20:4238-4250. doi: 10.1016/j.csbj.2022.07.051. Epub 2022 Aug 5.
The inflation of SARS-CoV-2 lineages with a high number of accumulated mutations (such as the recent case of Omicron) has risen concerns about the evolutionary capacity of this virus. Here, we propose a computational study to examine non-synonymous mutations gathered within genomes of SARS-CoV-2 from the beginning of the pandemic until February 2022. We provide both qualitative and quantitative descriptions of such corpus, focusing on statistically significant co-occurring and mutually exclusive mutations within single genomes. Then, we examine in depth the distributions of mutations over defined lineages and compare those of frequently co-occurring mutation pairs. Based on this comparison, we study mutations' convergence/divergence on the phylogenetic tree. As a result, we identify 1,818 co-occurring pairs of non-synonymous mutations showing at least one event of convergent evolution and 6,625 co-occurring pairs with at least one event of divergent evolution. Notable examples of both types are shown by means of a tree-based representation of lineages, visually capturing mutations' behaviors. Our method confirms several well-known cases; moreover, the provided evidence suggests that our workflow can explain aspects of the future mutational evolution of SARS-CoV-2.
具有大量累积突变的新冠病毒谱系（如最近的奥密克戎毒株）的出现引发了人们对该病毒进化能力的担忧。在此，我们提出一项计算研究，以检查自疫情开始至2022年2月期间新冠病毒基因组中积累的非同义突变。我们对这些数据进行了定性和定量描述，重点关注单个基因组中具有统计学意义的共现和互斥突变。然后，我们深入研究了突变在特定谱系中的分布，并比较了频繁共现的突变对的分布。基于这种比较，我们研究了突变在系统发育树上的趋同/分歧情况。结果，我们识别出1818对共现的非同义突变对，它们至少显示出一次趋同进化事件，以及6625对共现的非同义突变对，它们至少显示出一次分歧进化事件。通过基于谱系的树形表示展示了这两种类型的显著例子，直观地呈现了突变的行为。我们的方法证实了几个众所周知的案例；此外，所提供的证据表明我们的工作流程可以解释新冠病毒未来突变进化的一些方面。
