Transcriptomic Biomarkers to Discriminate Bacterial from Nonbacterial Infection in Adults Hospitalized with Respiratory Illness.
Transcriptomic Biomarkers to Discriminate Bacterial from Nonbacterial Infection in Adults Hospitalized with Respiratory Illness.
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DOI：
10.1038/s41598-017-06738-3
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发表时间：
2017-07-26
影响因子：
4.6
通讯作者：
Falsey AR
中科院分区：
文献类型：
--
作者：
Bhattacharya S;Rosenberg AF;Peterson DR;Grzesik K;Baran AM;Ashton JM;Gill SR;Corbett AM;Holden-Wiltse J;Topham DJ;Walsh EE;Mariani TJ;Falsey AR
下呼吸道感染（LRTI）通常导致成人住院治疗。由于细菌诊断测试不准确，抗生素经常被处方。外周血基因表达鉴定细菌感染是一种很有前途的策略。我们使用RNASeq评估了全血分析，以区分患有微生物学定义的LRTI的成人中的感染因子。招募有LRTI症状的住院成人。收集临床数据和血液，并进行全面的微生物检测。使用RNASeq和qPCR测量基因表达。使用Bonferroni校正的Wilcoxon检验鉴定区分细菌感染的基因。使用筛选的LASSO拟合预测细菌感染的约束逻辑模型。我们招募了94名被微生物学分类的受试者; 53名为“非细菌”，41名为“细菌”。RNAseq和qPCR证实了先前鉴定为区分细菌LRTI的10个基因的平均表达的显著差异。一种新的降维策略选择了包括11个基因的3个途径（淋巴细胞、α-亚油酸代谢、IGF调节）作为区分细菌感染的最佳标志物（naïve AUC = 0.94; nested CV-AUC = 0.86）。使用这些基因，我们构建了一个细菌LRTI的分类器，灵敏度为90%（79%CV），特异性为83%（76%CV）。这种新的，基于途径的基因集显示出作为区分细菌和非细菌LRTI的方法的希望。
Lower respiratory tract infection (LRTI) commonly causes hospitalization in adults. Because bacterial diagnostic tests are not accurate, antibiotics are frequently prescribed. Peripheral blood gene expression to identify subjects with bacterial infection is a promising strategy. We evaluated whole blood profiling using RNASeq to discriminate infectious agents in adults with microbiologically defined LRTI. Hospitalized adults with LRTI symptoms were recruited. Clinical data and blood was collected, and comprehensive microbiologic testing performed. Gene expression was measured using RNASeq and qPCR. Genes discriminatory for bacterial infection were identified using the Bonferroni-corrected Wilcoxon test. Constrained logistic models to predict bacterial infection were fit using screened LASSO. We enrolled 94 subjects who were microbiologically classified; 53 as “non-bacterial” and 41 as “bacterial”. RNAseq and qPCR confirmed significant differences in mean expression for 10 genes previously identified as discriminatory for bacterial LRTI. A novel dimension reduction strategy selected three pathways (lymphocyte, α-linoleic acid metabolism, IGF regulation) including eleven genes as optimal markers for discriminating bacterial infection (naïve AUC = 0.94; nested CV-AUC = 0.86). Using these genes, we constructed a classifier for bacterial LRTI with 90% (79% CV) sensitivity and 83% (76% CV) specificity. This novel, pathway-based gene set displays promise as a method to distinguish bacterial from nonbacterial LRTI.
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DOI：
10.1093/bioinformatics/btu638
发表时间：
2015-01-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Anders S;Pyl PT;Huber W
通讯作者：
Huber W
影响因子：
5.4
作者：
Chaussabel D;Pascual V;Banchereau J
通讯作者：
Banchereau J
影响因子：
15.1
作者：
Parnell, Grant P.;McLean, Anthony S.;Tang, Benjamin M.
通讯作者：
Tang, Benjamin M.
影响因子：
20.3
作者：
Ramilo, Octavio;Allman, Windy;Chaussabel, Damien
通讯作者：
Chaussabel, Damien
影响因子：
3.2
作者：
Blasi, Francesco;Stolz, Daiana;Piffer, Federico
通讯作者：
Piffer, Federico