Airway gene-expression classifiers for respiratory syncytial virus (RSV) disease severity in infants.
Airway gene-expression classifiers for respiratory syncytial virus (RSV) disease severity in infants.
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DOI：
10.1186/s12920-021-00913-2
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发表时间：
2021-02-25
影响因子：
2.7
通讯作者：
Qiu X
中科院分区：
文献类型：
--
作者：
Wang L;Chu CY;McCall MN;Slaunwhite C;Holden-Wiltse J;Corbett A;Falsey AR;Topham DJ;Caserta MT;Mariani TJ;Walsh EE;Qiu X
大量感染RSV的婴儿出现严重症状，需要住院治疗。我们目前缺乏与严重疾病相关的准确生物标志物。我们根据106例健康的RSV感染受试者在急性感染（发病第1-10天）和恢复期（发病第28天）的鼻刷样本的RNA测序，定义了气道基因表达谱。所有受试者均被分配了临床疾病严重程度评分（GRSS）。使用基于AIC的模型选择，我们建立了基于41个基因（NGSS 1）的GRSS稀疏线性相关。我们还建立了一个替代模型，该模型基于13个与急性严重感染相关但随时间推移显示稳定表达的基因（NGSS 2）。NGSS 1与疾病严重程度强相关，表明初始相关性（ρ）为ρ = 0.935，交叉验证相关性为0.813。作为二元分类器（轻度与重度），NGSS 1在交叉验证后正确分类了89.6%受试者的疾病严重程度。NGSS 2的准确性略低，但相当，交叉验证相关性为0.741，分类准确性为84.0%。在微创程序后获得的气道基因表达模式对于开发与原发性RSV感染中的疾病严重程度相关的临床有用的生物标志物具有潜在效用。在线版本包含补充材料，可通过10.1186/s12920-021-00913-2获得。
A substantial number of infants infected with RSV develop severe symptoms requiring hospitalization. We currently lack accurate biomarkers that are associated with severe illness. We defined airway gene expression profiles based on RNA sequencing from nasal brush samples from 106 full-tem previously healthy RSV infected subjects during acute infection (day 1–10 of illness) and convalescence stage (day 28 of illness). All subjects were assigned a clinical illness severity score (GRSS). Using AIC-based model selection, we built a sparse linear correlate of GRSS based on 41 genes (NGSS1). We also built an alternate model based upon 13 genes associated with severe infection acutely but displaying stable expression over time (NGSS2). NGSS1 is strongly correlated with the disease severity, demonstrating a naïve correlation (ρ) of ρ = 0.935 and cross-validated correlation of 0.813. As a binary classifier (mild versus severe), NGSS1 correctly classifies disease severity in 89.6% of the subjects following cross-validation. NGSS2 has slightly less, but comparable, accuracy with a cross-validated correlation of 0.741 and classification accuracy of 84.0%. Airway gene expression patterns, obtained following a minimally-invasive procedure, have potential utility for development of clinically useful biomarkers that correlate with disease severity in primary RSV infection. The online version contains supplementary material available at 10.1186/s12920-021-00913-2.
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DOI：
10.1093/infdis/jix400
发表时间：
2017-11-15
期刊：
The Journal of infectious diseases
影响因子：
--
作者：
Mariani TJ;Qiu X;Chu C;Wang L;Thakar J;Holden-Wiltse J;Corbett A;Topham DJ;Falsey AR;Caserta MT;Walsh EE
通讯作者：
Walsh EE
影响因子：
6.4
作者：
Caserta, Mary T.;Qiu, Xing;Walsh, Edward E.
通讯作者：
Walsh, Edward E.
DOI：
10.1056/nejmoa0804877
发表时间：
2009-02-05
期刊：
The New England journal of medicine
影响因子：
--
作者：
Hall CB;Weinberg GA;Iwane MK;Blumkin AK;Edwards KM;Staat MA;Auinger P;Griffin MR;Poehling KA;Erdman D;Grijalva CG;Zhu Y;Szilagyi P
通讯作者：
Szilagyi P
影响因子：
3.3
作者：
Arlot, Sylvain;Celisse, Alain
通讯作者：
Celisse, Alain
通过替代变量分析捕获基因表达研究中的异质性。
影响因子：
4.5
作者：
Leek, Jeffrey T.;Storey, John D.
通讯作者：
Storey, John D.