Gene expression-based classifiers identify Staphylococcus aureus infection in mice and humans
| Autor: | Ephraim L. Tsalik, Stephen F. Kingsmore, Sun Hee Ahn, Derek D. Cyr, Charles B. Cairns, Christopher W. Woods, Emanuel P. Rivers, Seth W. Glickman, Joseph Lucas, Vance G. Fowler, Aimee K. Zaas, Ronny M. Otero, Yurong Zhang, Jennifer C. van Velkinburgh, Geoffrey S. Ginsburg, Tim Veldman, Raymond J. Langley |
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| Jazyk: | angličtina |
| Rok vydání: | 2013 |
| Předmět: |
Bacterial Diseases
Critical Care and Emergency Medicine lcsh:Medicine medicine.disease_cause Mice 0302 clinical medicine Inbred strain Mice Inbred NOD Gene expression Genetics of the Immune System lcsh:Science Pathogen Immune Response Oligonucleotide Array Sequence Analysis Aged 80 and over 0303 health sciences Mice Inbred BALB C Mice Inbred C3H Escherichia Coli Multidisciplinary biology Middle Aged Staphylococcal Infections Clinical Laboratory Sciences 3. Good health Anti-Bacterial Agents Infectious Diseases Staphylococcus aureus 030220 oncology & carcinogenesis Host-Pathogen Interactions Medicine Research Article Adult Mice 129 Strain Mice Inbred Strains Staphylococcal infections Sensitivity and Specificity Microbiology Sepsis 03 medical and health sciences Young Adult Species Specificity Diagnostic Medicine Escherichia medicine Animals Humans 030304 developmental biology Aged Clinical Genetics Gene Expression Profiling lcsh:R Personalized Medicine Reproducibility of Results Bloodstream Infections biology.organism_classification medicine.disease Gene expression profiling Mice Inbred C57BL Immunology Clinical Immunology lcsh:Q |
| Zdroj: | PLoS ONE, Vol 8, Iss 1, p e48979 (2013) PLoS ONE |
| ISSN: | 1932-6203 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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