Gene expression-based classifiers identify Staphylococcus aureus infection in mice and humans.

Ahn, Sun Hee

Tsalik, Ephraim L

Cyr, Derek D

Zhang, Yurong

van Velkinburgh, Jennifer C

Langley, Raymond J

Glickman, Seth W

Cairns, Charles B

Zaas, Aimee K

Rivers, Emanuel P

Otero, Ronny M

Veldman, Tim

Kingsmore, Stephen F

Kingsmore, Stephen F

Lucas, Joseph

Woods, Christopher W

Ginsburg, Geoffrey S

Fowler, Vance G

Otto, Michael

United States

2017-01-01T20:12:04Z

2013

Staphylococcus aureus causes a spectrum of human infection. Diagnostic delays and uncertainty lead to treatment delays and inappropriate antibiotic use. A growing literature suggests the host's inflammatory response to the pathogen represents a potential tool to improve upon current diagnostics. The hypothesis of this study is that the host responds differently to S. aureus than to E. coli infection in a quantifiable way, providing a new diagnostic avenue. This study uses Bayesian sparse factor modeling and penalized binary regression to define peripheral blood gene-expression classifiers of murine and human S. aureus infection. The murine-derived classifier distinguished S. aureus infection from healthy controls and Escherichia coli-infected mice across a range of conditions (mouse and bacterial strain, time post infection) and was validated in outbred mice (AUC>0.97). A S. aureus classifier derived from a cohort of 94 human subjects distinguished S. aureus blood stream infection (BSI) from healthy subjects (AUC 0.99) and E. coli BSI (AUC 0.84). Murine and human responses to S. aureus infection share common biological pathways, allowing the murine model to classify S. aureus BSI in humans (AUC 0.84). Both murine and human S. aureus classifiers were validated in an independent human cohort (AUC 0.95 and 0.92, respectively). The approach described here lends insight into the conserved and disparate pathways utilized by mice and humans in response to these infections. Furthermore, this study advances our understanding of S. aureus infection; the host response to it; and identifies new diagnostic and therapeutic avenues.

http://www.ncbi.nlm.nih.gov/pubmed/23326304

PONE-D-12-25216

1932-6203

https://hdl.handle.net/10161/13321

eng

Public Library of Science (PLoS)

PLoS One

10.1371/journal.pone.0048979

Adult

Aged

Aged, 80 and over

Animals

Anti-Bacterial Agents

Gene Expression Profiling

Host-Pathogen Interactions

Humans

Mice

Mice, 129 Strain

Mice, Inbred BALB C

Mice, Inbred C3H

Mice, Inbred C57BL

Mice, Inbred NOD

Mice, Inbred Strains

Middle Aged

Oligonucleotide Array Sequence Analysis

Reproducibility of Results

Sensitivity and Specificity

Sepsis

Species Specificity

Staphylococcal Infections

Staphylococcus aureus

Young Adult

Gene expression-based classifiers identify Staphylococcus aureus infection in mice and humans.

Journal article

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

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

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

Fowler, Vance G|0000-0002-8048-0897

http://www.ncbi.nlm.nih.gov/pubmed/23326304

e48979

1

Basic Science Departments

Biomedical Engineering

Biostatistics & Bioinformatics

Clinical Science Departments

Duke

Duke Cancer Institute

Duke Clinical Research Institute

Global Health Institute

Institutes and Centers

Institutes and Provost's Academic Units

Medicine

Medicine, Cardiology

Medicine, Infectious Diseases

Molecular Genetics and Microbiology

Pathology

Pratt School of Engineering

School of Medicine

School of Nursing

School of Nursing - Secondary Group

Social Science Research Institute

University Institutes and Centers

Published

8