论文标题

全球分析超过50,000个SARS-COV-2基因组揭示了8个病毒基因之间的上毒

Global analysis of more than 50,000 SARS-Cov-2 genomes reveals epistasis between 8 viral genes

论文作者

Zeng, Hong-Li, Dichio, Vito, Horta, Edwin Rodríguez, Thorell, Kaisa, Aurell, Erik

论文摘要

全基因组上学分析是推断基因相互作用的强大工具,可以指导药物和疫苗发育并更深入地了解微生物发病机理。我们已经考虑了沉积在GISAID存储库中的所有完整的SARS-COV-2基因组,直到\ textBf {四}不同的截止日期,并使用直接耦合分析以及假设准链式平衡的假设来推断出对多型位点的适应性对适应性的依赖性贡献。我们发现\ textbf {八个}相互作用,其中三个位点位于基因ORF3A中,两个基因座都有非同义突变的基因座。我们还发现基因NSP13中两个基因座之间的相互作用,既有非同义突变,又有四个涉及一个含有同义突变的基因座的相互作用。总体而言,我们推断了病毒基因ORF3A和NSP2,NSP12和NSP6,ORF8和NSP4之间的基因座之间的相互作用,以及基因NSP2,NSP13和NSP14中的基因座。该论文打开了使用上位链接的显着联系的前景,作为寻找重组病毒病原体组合弱点的起点。

Genome-wide epistasis analysis is a powerful tool to infer gene interactions, which can guide drug and vaccine development and lead to a deeper understanding of microbial pathogenesis. We have considered all complete SARS-CoV-2 genomes deposited in the GISAID repository until \textbf{four} different cut-off dates, and used Direct Coupling Analysis together with an assumption of Quasi-Linkage Equilibrium to infer epistatic contributions to fitness from polymorphic loci. We find \textbf{eight} interactions, of which three between pairs where one locus lies in gene ORF3a, both loci holding non-synonymous mutations. We also find interactions between two loci in gene nsp13, both holding non-synonymous mutations, and four interactions involving one locus holding a synonymous mutation. Altogether we infer interactions between loci in viral genes ORF3a and nsp2, nsp12 and nsp6, between ORF8 and nsp4, and between loci in genes nsp2, nsp13 and nsp14. The paper opens the prospect to use prominent epistatically linked pairs as a starting point to search for combinatorial weaknesses of recombinant viral pathogens.

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