Gene expression-based classifiers identify Staphylococcus aureus infection in mice and humans.
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...
| Main Authors: | , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2013-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3541361?pdf=render |
| _version_ | 1818550556181921792 |
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| author | Sun Hee Ahn Ephraim L Tsalik Derek D Cyr Yurong Zhang Jennifer C van Velkinburgh Raymond J Langley Seth W Glickman Charles B Cairns Aimee K Zaas Emanuel P Rivers Ronny M Otero Tim Veldman Stephen F Kingsmore Stephen F Kingsmore Joseph Lucas Christopher W Woods Geoffrey S Ginsburg Vance G Fowler |
| author_facet | Sun Hee Ahn Ephraim L Tsalik Derek D Cyr Yurong Zhang Jennifer C van Velkinburgh Raymond J Langley Seth W Glickman Charles B Cairns Aimee K Zaas Emanuel P Rivers Ronny M Otero Tim Veldman Stephen F Kingsmore Stephen F Kingsmore Joseph Lucas Christopher W Woods Geoffrey S Ginsburg Vance G Fowler |
| author_sort | Sun Hee Ahn |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-12T08:48:02Z |
| format | Article |
| id | doaj.art-8b7bdab08eb242da8f6a8dd9d8b90b8d |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-12T08:48:02Z |
| publishDate | 2013-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-8b7bdab08eb242da8f6a8dd9d8b90b8d2022-12-22T00:30:22ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-0181e4897910.1371/journal.pone.0048979Gene expression-based classifiers identify Staphylococcus aureus infection in mice and humans.Sun Hee AhnEphraim L TsalikDerek D CyrYurong ZhangJennifer C van VelkinburghRaymond J LangleySeth W GlickmanCharles B CairnsAimee K ZaasEmanuel P RiversRonny M OteroTim VeldmanStephen F KingsmoreStephen F KingsmoreJoseph LucasChristopher W WoodsGeoffrey S GinsburgVance G FowlerStaphylococcus 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://europepmc.org/articles/PMC3541361?pdf=render |
| spellingShingle | Sun Hee Ahn Ephraim L Tsalik Derek D Cyr Yurong Zhang Jennifer C van Velkinburgh Raymond J Langley Seth W Glickman Charles B Cairns Aimee K Zaas Emanuel P Rivers Ronny M Otero Tim Veldman Stephen F Kingsmore Stephen F Kingsmore Joseph Lucas Christopher W Woods Geoffrey S Ginsburg Vance G Fowler Gene expression-based classifiers identify Staphylococcus aureus infection in mice and humans. PLoS ONE |
| title | Gene expression-based classifiers identify Staphylococcus aureus infection in mice and humans. |
| title_full | Gene expression-based classifiers identify Staphylococcus aureus infection in mice and humans. |
| title_fullStr | Gene expression-based classifiers identify Staphylococcus aureus infection in mice and humans. |
| title_full_unstemmed | Gene expression-based classifiers identify Staphylococcus aureus infection in mice and humans. |
| title_short | Gene expression-based classifiers identify Staphylococcus aureus infection in mice and humans. |
| title_sort | gene expression based classifiers identify staphylococcus aureus infection in mice and humans |
| url | http://europepmc.org/articles/PMC3541361?pdf=render |
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