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Series GSE33341 Query DataSets for GSE33341
Status Public on Jan 11, 2013
Title Gene Expression-Based Classifiers Identify Staphylococcus aureus Infection in Mice and Humans
Organisms Homo sapiens; Mus musculus
Experiment type Expression profiling by array
Summary 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 95 human subjects distinguished S. aureus blood stream infection (BSI) from healthy subjects (AUC 0.99) and E. coli BSI (AUC 0.82). 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 0.94, 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.
 
Overall design To create a host gene expression-based classifier for S. aureus infection, mice from a variety of experimental conditions were utilized. Seven different strains of inbred mice (n=187 total) were challenged with four different S. aureus strains via intraperitoneal inoculation and sacrificed at various time points as described in Methods. The comparator group for model derivation included 50 A/J or C57BL/6J mice inoculated with E. coli (O18:K1:H7) as well as 54 uninfected mice. Next, the murine S. aureus classifier was externally validated in outbred CD-1 mice with S. aureus infection (Sanger 476 or USA300), E. coli infection (O18:K1:H7), or uninfected controls (10 animals per condition). Method: All experiments were performed on mice 6-8 weeks old. For the murine S. aureus predictor, seven inbred mouse strains (3 mice/strain: 129S1/SvImJ, A/J, AKR/J, BALB/cByJ, C57BL/6J, C3H/HeJ, and NOD/LtJ) were IP inoculated with 107 CFU/g of S. aureus Sanger476, euthanized at 2h after injection, and bled. This was repeated using four different S. aureus strains (USA100, USA300, MW2, and Sanger476) in A/J mice (n=3 per S. aureus strain). For time series experiments, both A/J and C57BL/6J mouse strains were IP inoculated with S. aureus Sanger476 as above, and sacrificed at 2, 4, 6, and 12h after injection (n=5 per time point).
 
Contributor(s) Ahn SH, Tsalik EL, Cyr D, Zhang Y, Langley RJ, van Velkinburgh JC, Glickman SW, Cairns CB, Zaas AK, Rivers EP, Otero RM, Kingsmore SF, Lucas J, Woods CW, Veldman T, Ginsburg GS, Fowler VG
Citation(s) 23326304
Submission date Oct 31, 2011
Last update date Feb 11, 2019
Contact name Sun Hee Ahn
Organization name Duke University
Department Medicine
Lab Infectious Diseases (Staphylococcal Disease)
Street address Stead Bldg, RM 1546A
City Durham
State/province NC
ZIP/Postal code 27710
Country USA
 
Platforms (2)
GPL571 [HG-U133A_2] Affymetrix Human Genome U133A 2.0 Array
GPL1261 [Mouse430_2] Affymetrix Mouse Genome 430 2.0 Array
Samples (321)
GSM824455 blood 129S1/SvImJ 0hrs rep1 batch 2 batch 2 1545_4182_21995_129-cont-1set
GSM824456 blood 129S1/SvImJ 0hrs rep2 batch 2 batch 2 1545_4182_22009_129-cont-2set
GSM824457 blood 129S1/SvImJ 0hrs rep3 batch 2 batch 2 1545_4182_22023_129-cont-3set
Relations
BioProject PRJNA148969

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE33341_RAW.tar 1.0 Gb (http)(custom) TAR (of CEL, CHP)
Processed data included within Sample table
Processed data provided as supplementary file
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