SMDP：用于快速估计异常谱系突变史的SARS-CoV-2突变分布分析器
SMDP: SARS-CoV-2 Mutation Distribution Profiler for rapid estimation of mutational histories of unusual lineages
AI总结：
本文开发了开源Web应用SMDP，通过比对用户提交的SARS-CoV-2突变列表与多种已知突变分布，快速推断异常谱系的进化史并评估药物诱导突变的证据，以辅助公共卫生风险评估。
摘要：
SARS-CoV-2通常随时间以相对恒定的速率进化。然而，偶尔会出现相对于采样日期具有超出预期突变数量的谱系。此类谱系的出现有多种原因，包括慢性感染期间进化施加的选择压力，或暴露于如molnupiravir等诱导突变的药物。我们开发了一款开源的基于Web的应用程序（SMDP: SARS-CoV-2 Mutation Distribution Profiler；https://eringill.shinyapps.io/covid_mutation_distributions），它将用户提交的谱系定义突变列表或包含单一基因组的FASTA文件（从中计算谱系定义突变）与已建立的突变分布进行比较，这些分布包括在以下情况中观察到的分布：（1）大流行的前九个月，（2）Omicron的全球传播期间，（3）免疫缺陷患者的慢性感染期间，以及（4）从人类到鹿的人畜共患外溢期间。该应用程序为用户的突变列表计算最可能的分布，并显示所有分布的对数似然值。此外，还计算用户列表的转换：颠换比率，以确定是否有证据表明暴露于如molnupiravir等诱导突变的药物，并指示列表中是否包含nsp14校对结构域中的突变，这可能导致该谱系具有高于预期的突变率。此工具将有助于公共卫生人员和研究人员快速推断SARS-CoV-2变体的进化史，从而辅助风险评估和公共卫生应对。
英文摘要：
SARS-CoV-2 usually evolves at a relatively constant rate over time. Occasionally, however, lineages arise with higher-than-expected numbers of mutations given the date of sampling. Such lineages can arise for a variety of reasons, including selection pressures imposed by evolution during a chronic infection or exposure to mutation-inducing drugs like molnupiravir. We have developed an open-source web-based application (SMDP: SARS-CoV-2 Mutation Distribution Profiler; https://eringill.shinyapps.io/covid_mutation_distributions) that compares a list of user-submitted lineage-defining mutations or a FASTA file containing a single genome (from which lineage-defining mutations are calculated) with established mutation distributions including those observed during (1) the first nine months of the pandemic, (2) during the global transmission of Omicron, (3) during the chronic infection of immunocompromised patients, and (4) during zoonotic spillover from humans to deer. The application calculates the most likely distribution for the user's mutation list and displays log likelihoods for all distributions. In addition, the transition:transversion ratio of the user's list is calculated to determine whether there is evidence of exposure to a mutation-inducing drug such as molnupiravir and indicates whether the list contains mutations in the proofreading domain of nsp14 which could lead to a higher-than-expected mutation rate in the lineage. This tool will be useful for public health and researchers seeking to rapidly infer evolutionary histories of SARS-CoV-2 variants, which can aid risk assessment and public health responses.
机构、总结、中文摘要均由AI分析而来，可能存在错误，请以论文正文为准。
