Analysis of 6.4 million SARS-CoV-2 genomes identifies mutations associated with fitness.

Analysis of 6.4 million SARS-CoV-2 genomes identifies mutations associated with fitness.
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对640万个SARS-CoV-2基因组的分析确定了与健康相关的突变。

DOI:
10.1126/science.abm1208
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发表时间:
2022-06-17
期刊:
Science (New York, N.Y.)
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随着适应性的增加,SARS-CoV-2变异株的反复出现突显了快速检测和表征新谱系的价值。我们开发了一种层次化贝叶斯多项Logistic回归模型PyR0,该模型可以推断地理区域内所有病毒谱系的相对流行率,检测流行率增加的谱系,并识别与适应度相关的突变。将PyR0应用于所有公开可用的SARS-CoV-2基因组,我们发现了许多可以提高适应度的替换,包括先前发现的尖峰突变和核衣壳和非结构蛋白中的许多非尖峰突变。PyR0根据新谱系的突变情况预测新谱系的增长,在新序列可用时对谱系的适合度进行排名,并优先考虑生物学和公共卫生方面的突变以进行功能表征。
Repeated emergence of SARS-CoV-2 variants with increased fitness underscores the value of rapid detection and characterization of new lineages. We have developed PyR0, a hierarchical Bayesian multinomial logistic regression model that infers relative prevalence of all viral lineages across geographic regions, detects lineages increasing in prevalence, and identifies mutations relevant to fitness. Applying PyR0 to all publicly available SARS-CoV-2 genomes, we identify numerous substitutions that increase fitness, including previously identified spike mutations and many non-spike mutations within the nucleocapsid and nonstructural proteins. PyR0 forecasts growth of new lineages from their mutational profile, ranks the fitness of lineages as new sequences become available, and prioritizes mutations of biological and public health concern for functional characterization.
SARS-COV-2血统的估计可传播和影响B.1.1.7在英国。
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期刊: Science (New York, N.Y.)
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