Host Gene Expression in Nose and Blood for the Diagnosis of Viral Respiratory Infection

Host Gene Expression in Nose and Blood for the Diagnosis of Viral Respiratory Infection
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DOI:
10.1093/infdis/jiy608
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发表时间:
2019-04-01
影响因子:
6.4
通讯作者:
Storch, Gregory A.
Storch, Gregory A.
中科院分区:
医学2区
文献类型:
--
作者:
Yu, Jinsheng;Peterson, Derick R.;Storch, Gregory A.

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背景最近,越来越多的人对宿主转录组学分析的潜力感兴趣,以增强传染病的诊断。我们比较了鼻和血液样本,以评估急性呼吸道合胞病毒(RSV)感染、症状性非RSV呼吸道病毒感染、无症状鼻病毒感染和病毒阴性无症状对照儿童的宿主转录组学反应。我们使用嵌套的留一对交叉验证和监督主成分分析来定义小的基因集,其表达模式准确地将受试者分类。我们使用外部数据集验证了基因分类得分。尽管鼻RNA的质量较低,但在每种样品类型中通过微阵列检测到的基因数量是相等的。鼻基因表达信号主要来源于上皮细胞,但也包括可变的白细胞贡献。病毒感染儿童中表达增加的基因数量在鼻和血液样本中相当,而鼻样本中许多与纤毛功能和组装相关的基因表达也减少。鼻基因表达特征在区分有症状、无症状和未感染儿童方面同样好或更好。我们的结果支持使用鼻样本来加强基于病原体的测试来诊断病毒性呼吸道感染。
Background. Recently there has been a growing interest in the potential for host transcriptomic analysis to augment the diagnosis of infectious diseases.Methods. We compared nasal and blood samples for evaluation of the host transcriptomic response in children with acute respiratory syncytial virus (RSV) infection, symptomatic non-RSV respiratory virus infection, asymptomatic rhinovirus infection, and virus-negative asymptomatic controls. We used nested leave-one-pair-out cross-validation and supervised principal components analysis to define small sets of genes whose expression patterns accurately classified subjects. We validated gene classification scores using an external data set.Results. Despite lower quality of nasal RNA, the number of genes detected by microarray in each sample type was equivalent. Nasal gene expression signal derived mainly from epithelial cells but also included a variable leukocyte contribution. The number of genes with increased expression in virus-infected children was comparable in nasal and blood samples, while nasal samples also had decreased expression of many genes associated with ciliary function and assembly. Nasal gene expression signatures were as good or better for discriminating between symptomatic, asymptomatic, and uninfected children.Conclsusions. Our results support the use of nasal samples to augment pathogen-based tests to diagnose viral respiratory infection.