A miRNA Host Response Signature Accurately Discriminates Acute Respiratory Infection Etiologies.

Poore, Gregory D

Ko, Emily R

Valente, Ashlee

Henao, Ricardo

Sumner, Kelsey

Hong, Christopher

Burke, Thomas W

Nichols, Marshall

McClain, Micah T

Huang, Erich S

Ginsburg, Geoffrey S

Woods, Christopher W

Tsalik, Ephraim L

2020-11-01T14:38:29Z

2020-11-01T14:38:29Z

2018-01

2020-11-01T14:38:26Z

Background: Acute respiratory infections (ARIs) are the leading indication for antibacterial prescriptions despite a viral etiology in the majority of cases. The lack of available diagnostics to discriminate viral and bacterial etiologies contributes to this discordance. Recent efforts have focused on the host response as a source for novel diagnostic targets although none have explored the ability of host-derived microRNAs (miRNA) to discriminate between these etiologies. Methods: In this study, we compared host-derived miRNAs and mRNAs from human H3N2 influenza challenge subjects to those from patients with Streptococcus pneumoniae pneumonia. Sparse logistic regression models were used to generate miRNA signatures diagnostic of ARI etiologies. Generalized linear modeling of mRNAs to identify differentially expressed (DE) genes allowed analysis of potential miRNA:mRNA relationships. High likelihood miRNA:mRNA interactions were examined using binding target prediction and negative correlation to further explore potential changes in pathway regulation in response to infection. Results: The resultant miRNA signatures were highly accurate in discriminating ARI etiologies. Mean accuracy was 100% [88.8-100; 95% Confidence Interval (CI)] in discriminating the healthy state from S. pneumoniae pneumonia and 91.3% (72.0-98.9; 95% CI) in discriminating S. pneumoniae pneumonia from influenza infection. Subsequent differential mRNA gene expression analysis revealed alterations in regulatory networks consistent with known biology including immune cell activation and host response to viral infection. Negative correlation network analysis of miRNA:mRNA interactions revealed connections to pathways with known immunobiology such as interferon regulation and MAP kinase signaling. Conclusion: We have developed novel human host-response miRNA signatures for bacterial and viral ARI etiologies. miRNA host response signatures reveal accurate discrimination between S. pneumoniae pneumonia and influenza etiologies for ARI and integrated analyses of the host-pathogen interface are consistent with expected biology. These results highlight the differential miRNA host response to bacterial and viral etiologies of ARI, offering new opportunities to distinguish these entities.

1664-302X

1664-302X

https://hdl.handle.net/10161/21657

eng

Frontiers Media SA

Frontiers in microbiology

10.3389/fmicb.2018.02957

bacterial infections

host-pathogen interaction

micro RNA

molecular diagnostics

personalized medicine

respiratory tract infections

transcriptome

viral infections

A miRNA Host Response Signature Accurately Discriminates Acute Respiratory Infection Etiologies.

Journal article

Henao, Ricardo|0000-0003-4980-845X

Burke, Thomas W|0000-0003-0592-5822

Huang, Erich S|0000-0001-5547-9408

Ginsburg, Geoffrey S|0000-0003-4739-9808

Woods, Christopher W|0000-0001-7240-2453

Tsalik, Ephraim L|0000-0002-6417-2042

2957

DEC

School of Medicine

Electrical and Computer Engineering

Duke Clinical Research Institute

Biostatistics & Bioinformatics

Duke

Pratt School of Engineering

Institutes and Centers

Basic Science Departments

Medicine, General Internal Medicine

Medicine

Clinical Science Departments

Staff

Medicine, Infectious Diseases

Duke Innovation & Entrepreneurship

Surgery

Initiatives

Institutes and Provost's Academic Units

Nursing

Duke Cancer Institute

Pathology

Medicine, Cardiology

School of Nursing

Duke Global Health Institute

University Institutes and Centers

Molecular Genetics and Microbiology

Published

9