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Host gene expression classifiers diagnose acute respiratory illness etiology
Journal article   Open access   Peer reviewed

Host gene expression classifiers diagnose acute respiratory illness etiology

Ephraim L Tsalik, Ricardo Henao, Marshall Nichols, Thomas Burke, Emily R Ko, Micah T McClain, Lori L Hudson, Anna Mazur, Debra H Freeman, Tim Veldman, …
Science translational medicine, v 8(322), pp 322ra11-322ra11
20 Jan 2016
PMID: 26791949
url
https://doi.org/10.1126/scitranslmed.aad6873View
Published, Version of Record (VoR) Open

Abstract

Adolescent Adult Aged Aged, 80 and over Case-Control Studies Child Child, Preschool Cohort Studies Coinfection - genetics Coinfection - microbiology Coinfection - virology Demography Female Gene Expression Regulation Host-Pathogen Interactions - genetics Humans Male Middle Aged Reproducibility of Results Respiratory Tract Infections - diagnosis Respiratory Tract Infections - genetics Respiratory Tract Infections - microbiology Respiratory Tract Infections - virology Signal Transduction - genetics Young Adult
Acute respiratory infections caused by bacterial or viral pathogens are among the most common reasons for seeking medical care. Despite improvements in pathogen-based diagnostics, most patients receive inappropriate antibiotics. Host response biomarkers offer an alternative diagnostic approach to direct antimicrobial use. This observational cohort study determined whether host gene expression patterns discriminate noninfectious from infectious illness and bacterial from viral causes of acute respiratory infection in the acute care setting. Peripheral whole blood gene expression from 273 subjects with community-onset acute respiratory infection (ARI) or noninfectious illness, as well as 44 healthy controls, was measured using microarrays. Sparse logistic regression was used to develop classifiers for bacterial ARI (71 probes), viral ARI (33 probes), or a noninfectious cause of illness (26 probes). Overall accuracy was 87% (238 of 273 concordant with clinical adjudication), which was more accurate than procalcitonin (78%, P < 0.03) and three published classifiers of bacterial versus viral infection (78 to 83%). The classifiers developed here externally validated in five publicly available data sets (AUC, 0.90 to 0.99). A sixth publicly available data set included 25 patients with co-identification of bacterial and viral pathogens. Applying the ARI classifiers defined four distinct groups: a host response to bacterial ARI, viral ARI, coinfection, and neither a bacterial nor a viral response. These findings create an opportunity to develop and use host gene expression classifiers as diagnostic platforms to combat inappropriate antibiotic use and emerging antibiotic resistance.

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Collaboration types
Domestic collaboration
Web of Science research areas
Cell Biology
Medicine, Research & Experimental
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