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SARS-CoV-2 基因组时间框架:死后间隔估计的概念验证。

A Timeframe for SARS-CoV-2 Genomes: A Proof of Concept for Postmortem Interval Estimations.

机构信息

Grupo de Investigacion en Genética, Vacunas, Infecciones y Pediatría (GENVIP), Hospital Clínico Universitario, Universidade de Santiago de Compostela, 15706 Santiago de Compostela, Galicia, Spain.

GenPoB Research Group, Instituto de Investigación Sanitaria (IDIS), Hospital Clínico Universitario de Santiago (SERGAS), 15706 Santiago de Compostela, Galicia, Spain.

出版信息

Int J Mol Sci. 2022 Oct 25;23(21):12899. doi: 10.3390/ijms232112899.

Abstract

Establishing the timeframe when a particular virus was circulating in a population could be useful in several areas of biomedical research, including microbiology and legal medicine. Using simulations, we demonstrate that the circulation timeframe of an unknown SARS-CoV-2 genome in a population (hereafter, estimated time of a queried genome [QG]; ) can be easily predicted using a phylogenetic model based on a robust reference genome database of the virus, and information on their sampling dates. We evaluate several phylogeny-based approaches, including modeling evolutionary (substitution) rates of the SARS-CoV-2 genome (~10 substitutions/nucleotide/year) and the mutational (substitutions) differences separating the QGs from the reference genomes (RGs) in the database. Owing to the mutational characteristics of the virus, the present Viral Molecular Clock Dating (VMCD) method covers timeframes going backwards from about a month in the past. The method has very low errors associated to the estimates and narrow intervals of , both ranging from a few days to a few weeks regardless of the mathematical model used. The SARS-CoV-2 model represents a proof of concept that can be extrapolated to any other microorganism, provided that a robust genome sequence database is available. Besides obvious applications in epidemiology and microbiology investigations, there are several contexts in forensic casework where estimating could be useful, including estimation of the postmortem intervals (PMI) and the dating of samples stored in hospital settings.

摘要

确定特定病毒在人群中传播的时间框架在几个生物医学研究领域可能是有用的,包括微生物学和法医学。通过模拟,我们证明,使用基于病毒稳健参考基因组数据库以及其采样日期的信息的基于系统发育的模型,可以轻松预测人群中未知 SARS-CoV-2 基因组的传播时间框架(以下简称,查询基因组的估计时间[QG])。我们评估了几种基于系统发育的方法,包括对 SARS-CoV-2 基因组的进化(替换)率建模(~10 个替换/核苷酸/年)以及从数据库中的参考基因组(RG)中分离 QG 的突变(替换)差异。由于病毒的突变特征,目前的病毒分子钟日期推断(VMCD)方法可以回溯到过去大约一个月的时间。该方法与 估计值相关的错误非常低,且 的估计范围很窄,无论使用哪种数学模型,范围都在几天到几周之间。SARS-CoV-2 模型代表了一个概念验证,可以推广到任何其他微生物,只要有一个稳健的基因组序列数据库即可。除了在流行病学和微生物学调查中的明显应用外,在法医案例工作中有几个情况下估计 可能是有用的,包括推断死后时间间隔(PMI)和估计存储在医院环境中的样本的日期。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fafe/9656715/c6a48de295df/ijms-23-12899-g004.jpg

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