Transcriptomic Biomarkers to Discriminate Bacterial from Nonbacterial Infection in Adults Hospitalized with Respiratory Illness

Abstract 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 evaluate...

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Autores principales:	Soumyaroop Bhattacharya, Alex F. Rosenberg, Derick R. Peterson, Katherine Grzesik, Andrea M. Baran, John M. Ashton, Steven R. Gill, Anthony M. Corbett, Jeanne Holden-Wiltse, David J. Topham, Edward E. Walsh, Thomas J. Mariani, Ann R. Falsey
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/ba1469c18a8948bdb99d2592622d6433
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spelling	oai:doaj.org-article:ba1469c18a8948bdb99d2592622d64332021-12-02T15:05:42ZTranscriptomic Biomarkers to Discriminate Bacterial from Nonbacterial Infection in Adults Hospitalized with Respiratory Illness10.1038/s41598-017-06738-32045-2322https://doaj.org/article/ba1469c18a8948bdb99d2592622d64332017-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-06738-3https://doaj.org/toc/2045-2322Abstract 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.Soumyaroop BhattacharyaAlex F. RosenbergDerick R. PetersonKatherine GrzesikAndrea M. BaranJohn M. AshtonSteven R. GillAnthony M. CorbettJeanne Holden-WiltseDavid J. TophamEdward E. WalshThomas J. MarianiAnn R. FalseyNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-12 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Soumyaroop Bhattacharya Alex F. Rosenberg Derick R. Peterson Katherine Grzesik Andrea M. Baran John M. Ashton Steven R. Gill Anthony M. Corbett Jeanne Holden-Wiltse David J. Topham Edward E. Walsh Thomas J. Mariani Ann R. Falsey Transcriptomic Biomarkers to Discriminate Bacterial from Nonbacterial Infection in Adults Hospitalized with Respiratory Illness
description	Abstract 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.
format	article
author	Soumyaroop Bhattacharya Alex F. Rosenberg Derick R. Peterson Katherine Grzesik Andrea M. Baran John M. Ashton Steven R. Gill Anthony M. Corbett Jeanne Holden-Wiltse David J. Topham Edward E. Walsh Thomas J. Mariani Ann R. Falsey
author_facet	Soumyaroop Bhattacharya Alex F. Rosenberg Derick R. Peterson Katherine Grzesik Andrea M. Baran John M. Ashton Steven R. Gill Anthony M. Corbett Jeanne Holden-Wiltse David J. Topham Edward E. Walsh Thomas J. Mariani Ann R. Falsey
author_sort	Soumyaroop Bhattacharya
title	Transcriptomic Biomarkers to Discriminate Bacterial from Nonbacterial Infection in Adults Hospitalized with Respiratory Illness
title_short	Transcriptomic Biomarkers to Discriminate Bacterial from Nonbacterial Infection in Adults Hospitalized with Respiratory Illness
title_full	Transcriptomic Biomarkers to Discriminate Bacterial from Nonbacterial Infection in Adults Hospitalized with Respiratory Illness
title_fullStr	Transcriptomic Biomarkers to Discriminate Bacterial from Nonbacterial Infection in Adults Hospitalized with Respiratory Illness
title_full_unstemmed	Transcriptomic Biomarkers to Discriminate Bacterial from Nonbacterial Infection in Adults Hospitalized with Respiratory Illness
title_sort	transcriptomic biomarkers to discriminate bacterial from nonbacterial infection in adults hospitalized with respiratory illness
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/ba1469c18a8948bdb99d2592622d6433
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Transcriptomic Biomarkers to Discriminate Bacterial from Nonbacterial Infection in Adults Hospitalized with Respiratory Illness

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