文献检索文档翻译深度研究
Suppr Zotero 插件Zotero 插件
邀请有礼套餐&价格历史记录

新学期,新优惠

限时优惠:9月1日-9月22日

30天高级会员仅需29元

1天体验卡首发特惠仅需5.99元

了解详情
不再提醒
插件&应用
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
高级版
套餐订阅购买积分包
AI 工具
文献检索文档翻译深度研究
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利:CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2025

从 PCR 数据预测传染性病毒的存在:非人类灵长类动物中 SARS-CoV-2 的荟萃分析。

Predicting the presence of infectious virus from PCR data: A meta-analysis of SARS-CoV-2 in non-human primates.

机构信息

Department of Ecology and Evolutionary Biology, University of California Los Angeles, Los Angeles, California, United States of America.

Department of Computational Medicine, University of California Los Angeles, Los Angeles, California, United States of America.

出版信息

PLoS Pathog. 2024 Apr 29;20(4):e1012171. doi: 10.1371/journal.ppat.1012171. eCollection 2024 Apr.


DOI:10.1371/journal.ppat.1012171
PMID:38683864
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11081500/
Abstract

Researchers and clinicians often rely on molecular assays like PCR to identify and monitor viral infections, instead of the resource-prohibitive gold standard of viral culture. However, it remains unclear when (if ever) PCR measurements of viral load are reliable indicators of replicating or infectious virus. The recent popularity of PCR protocols targeting subgenomic RNA for SARS-CoV-2 has caused further confusion, as the relationships between subgenomic RNA and standard total RNA assays are incompletely characterized and opinions differ on which RNA type better predicts culture outcomes. Here, we explore these issues by comparing total RNA, subgenomic RNA, and viral culture results from 24 studies of SARS-CoV-2 in non-human primates (including 2167 samples from 174 individuals) using custom-developed Bayesian statistical models. On out-of-sample data, our best models predict subgenomic RNA positivity from total RNA data with 91% accuracy, and they predict culture positivity with 85% accuracy. Further analyses of individual time series indicate that many apparent prediction errors may arise from issues with assay sensitivity or sample processing, suggesting true accuracy may be higher than these estimates. Total RNA and subgenomic RNA showed equivalent performance as predictors of culture positivity. Multiple cofactors (including exposure conditions, host traits, and assay protocols) influence culture predictions, yielding insights into biological and methodological sources of variation in assay outcomes-and indicating that no single threshold value applies across study designs. We also show that our model can accurately predict when an individual is no longer infectious, illustrating the potential for future models trained on human data to guide clinical decisions on case isolation. Our work shows that meta-analysis of in vivo data can overcome longstanding challenges arising from limited sample sizes and can yield robust insights beyond those attainable from individual studies. Our analytical pipeline offers a framework to develop similar predictive tools in other virus-host systems, including models trained on human data, which could support laboratory analyses, medical decisions, and public health guidelines.

摘要

研究人员和临床医生经常依赖聚合酶链反应(PCR)等分子检测方法来识别和监测病毒感染,而不是采用资源密集型的病毒培养作为金标准。然而,PCR 病毒载量测量值何时(如果有)能够可靠地指示复制或感染性病毒,目前仍不清楚。最近针对 SARS-CoV-2 的亚基因组 RNA 的 PCR 方案变得流行,这进一步造成了混淆,因为亚基因组 RNA 与标准总 RNA 检测之间的关系尚未完全确定,并且对于哪种 RNA 类型更能预测培养结果的意见也存在分歧。在这里,我们通过使用定制的贝叶斯统计模型,比较了来自非人类灵长类动物 24 项 SARS-CoV-2 研究的总 RNA、亚基因组 RNA 和病毒培养结果(包括来自 174 个人的 2167 个样本)。在样本外数据上,我们最好的模型可以以 91%的准确度从总 RNA 数据预测亚基因组 RNA 阳性,并且可以以 85%的准确度预测培养阳性。对个别时间序列的进一步分析表明,许多明显的预测错误可能源于检测灵敏度或样本处理方面的问题,这表明真实的准确性可能高于这些估计。总 RNA 和亚基因组 RNA 作为培养阳性的预测因子表现相当。多个协变量(包括暴露条件、宿主特征和检测方案)影响培养预测,为检测结果的生物学和方法学来源提供了深入了解,并表明没有单一的阈值值适用于所有研究设计。我们还表明,我们的模型可以准确预测个体何时不再具有传染性,这说明了未来基于人类数据训练的模型在指导病例隔离的临床决策方面的潜力。我们的工作表明,对体内数据的荟萃分析可以克服由于样本量有限而导致的长期挑战,并产生超越个别研究所能获得的稳健见解。我们的分析管道为在其他病毒-宿主系统中开发类似的预测工具提供了一个框架,包括基于人类数据训练的模型,这些模型可以支持实验室分析、医疗决策和公共卫生指南。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9ea8/11081500/117e285f99e1/ppat.1012171.g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9ea8/11081500/040ed53756b8/ppat.1012171.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9ea8/11081500/6dacf2273332/ppat.1012171.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9ea8/11081500/724ac0ca6e41/ppat.1012171.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9ea8/11081500/06c8c1a59857/ppat.1012171.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9ea8/11081500/cf2a9747256e/ppat.1012171.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9ea8/11081500/f32ea488bc78/ppat.1012171.g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9ea8/11081500/117e285f99e1/ppat.1012171.g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9ea8/11081500/040ed53756b8/ppat.1012171.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9ea8/11081500/6dacf2273332/ppat.1012171.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9ea8/11081500/724ac0ca6e41/ppat.1012171.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9ea8/11081500/06c8c1a59857/ppat.1012171.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9ea8/11081500/cf2a9747256e/ppat.1012171.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9ea8/11081500/f32ea488bc78/ppat.1012171.g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9ea8/11081500/117e285f99e1/ppat.1012171.g007.jpg

相似文献

[1]
Predicting the presence of infectious virus from PCR data: A meta-analysis of SARS-CoV-2 in non-human primates.

PLoS Pathog. 2024-4

[2]
Diagnostic usefulness of subgenomic RNA detection of viable SARS-CoV-2 in patients with COVID-19.

Clin Microbiol Infect. 2022-1

[3]
SARS-CoV-2 Virus Culture, Genomic and Subgenomic RNA Load, and Rapid Antigen Test in Experimentally Infected Syrian Hamsters.

J Virol. 2022-9-28

[4]
Clinical evaluation of a multiplex real-time RT-PCR assay for detection of SARS-CoV-2 in individual and pooled upper respiratory tract samples.

Arch Virol. 2021-9

[5]
Digital droplet PCR accurately quantifies SARS-CoV-2 viral load from crude lysate without nucleic acid purification.

Sci Rep. 2021-1-12

[6]
Predicting infectivity: comparing four PCR-based assays to detect culturable SARS-CoV-2 in clinical samples.

EMBO Mol Med. 2022-2-7

[7]
Effectiveness and cost-effectiveness of four different strategies for SARS-CoV-2 surveillance in the general population (CoV-Surv Study): a structured summary of a study protocol for a cluster-randomised, two-factorial controlled trial.

Trials. 2021-1-8

[8]
Sensitive tracking of circulating viral RNA through all stages of SARS-CoV-2 infection.

J Clin Invest. 2021-4-1

[9]
RNA reference materials with defined viral RNA loads of SARS-CoV-2-A useful tool towards a better PCR assay harmonization.

PLoS One. 2022

[10]
Prolonged SARS-CoV-2 Positivity in Immunocompetent Patients: Virus Isolation, Genomic Integrity, and Transmission Risk.

Microbiol Spectr. 2021-12-22

本文引用的文献

[1]
Clinical utility of SARS-CoV-2 subgenomic RT-PCR in a pediatric quaternary care setting.

J Clin Virol. 2023-7

[2]
SARS-CoV-2 viral load and shedding kinetics.

Nat Rev Microbiol. 2023-3

[3]
SARS-CoV-2 Virus Culture, Genomic and Subgenomic RNA Load, and Rapid Antigen Test in Experimentally Infected Syrian Hamsters.

J Virol. 2022-9-28

[4]
Sars-Cov-2 antigen tests predict infectivity based on viral culture: comparison of antigen, PCR viral load, and viral culture testing on a large sample cohort.

Clin Microbiol Infect. 2023-1

[5]
Daily longitudinal sampling of SARS-CoV-2 infection reveals substantial heterogeneity in infectiousness.

Nat Microbiol. 2022-5

[6]
Surveillance and Correlation of Severe Acute Respiratory Syndrome Coronavirus 2 Viral RNA, Antigen, Virus Isolation, and Self-Reported Symptoms in a Longitudinal Study With Daily Sampling.

Clin Infect Dis. 2022-11-14

[7]
Safety, tolerability and viral kinetics during SARS-CoV-2 human challenge in young adults.

Nat Med. 2022-5

[8]
NIH issues a seismic mandate: share data publicly.

Nature. 2022-2

[9]
Predicting infectivity: comparing four PCR-based assays to detect culturable SARS-CoV-2 in clinical samples.

EMBO Mol Med. 2022-2-7

[10]
In vivo kinetics of SARS-CoV-2 infection and its relationship with a person's infectiousness.

Proc Natl Acad Sci U S A. 2021-12-7

文献AI研究员

20分钟写一篇综述,助力文献阅读效率提升50倍

立即体验

用中文搜PubMed

大模型驱动的PubMed中文搜索引擎

马上搜索

推荐工具

医学文档翻译智能文献检索