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

Soumyaroop Bhattacharya, Division of Neonatology and Pediatric Molecular and Personalized Medicine Program, Department of Pediatrics, University of Rochester School Medicine, Rochester, NY, USA.
Alex F. Rosenberg, Division of Allergy Immunology & Rheumatology, Department of Medicine, University of Rochester School Medicine, Rochester, NY, USA.
Derick R. Peterson, Department of Biostatistics and Computational Biology, University of Rochester School Medicine, Rochester, NY, USA.
Katherine Grzesik, Department of Biostatistics and Computational Biology, University of Rochester School Medicine, Rochester, NY, USA.
Andrea M. Baran, Department of Biostatistics and Computational Biology, University of Rochester School Medicine, Rochester, NY, USA.
John M. Ashton, Genomics Research Center, University of Rochester School Medicine, Rochester, NY, USA.
Steven R. Gill, Genomics Research Center, University of Rochester School Medicine, Rochester, NY, USA.
Anthony M. Corbett, Department of Biostatistics and Computational Biology, University of Rochester School Medicine, Rochester, NY, USA.
Jeanne Holden-Wiltse, Department of Biostatistics and Computational Biology, University of Rochester School Medicine, Rochester, NY, USA.
David J. Topham, David H. Smith Center for Vaccine Biology and Immunology, University of Rochester School Medicine, Rochester, NY, USA.
Edward E. Walsh, Rochester Regional HealthFollow
Thomas J. Mariani, Division of Neonatology and Pediatric Molecular and Personalized Medicine Program, Department of Pediatrics, University of Rochester School Medicine, Rochester, NY, USA.
Ann R. Falsey, Rochester Regional HealthFollow

Department

Infectious Diseases

Document Type

Article

Publication Title

Scientific Reports

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.

First Page

6548

DOI

10.1038/s41598-017-06738-3

Volume

7

Issue

1

Publication Date

7-26-2017

Medical Subject Headings

Adult; Aged; Aged, 80 and over; Bacterial Infections (diagnosis, pathology); Biomarkers (blood); Female; Gene Expression Profiling; Humans; Male; Middle Aged; Real-Time Polymerase Chain Reaction; Respiratory Tract Infections (diagnosis, pathology); Sensitivity and Specificity; Sequence Analysis, RNA

PubMed ID

28747714

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