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Series GSE15869 Query DataSets for GSE15869
Status Public on Apr 29, 2009
Title Host lung gene expression patterns predict the etiology of infectious pneumonias
Organism Mus musculus
Experiment type Expression profiling by array
Summary Rationale: Lower respiratory tract infections continue to exact unacceptable worldwide mortality, often because the infecting pathogen cannot be identified. The respiratory epithelia provide protection from pneumonias through organism-specific generation of antimicrobial products, offering potential insight into the identity of infecting pathogens. Objective: This study assesses the capacity of the host gene expression response to infection to predict lower respiratory pathogens without reliance on culture data. Methods: Mice were inhalationally challenged with S. pneumoniae, P. aeruginosa, A. fumigatus or PBS prior to whole genome gene expression microarray analysis of their pulmonary parenchyma. Characteristic gene expression patterns for each condition were identified, allowing the derivation of prediction rules for each pathogen. After confirming the predictive capacity of gene expression data in blinded challenges, a computerized algorithm was devised to predict the infectious conditions of subsequent subjects. Measurements and Main Results: We observed robust, pathogen-specific gene expression patterns as early as 2 h after infection. We were able to develop a predictive model that used a limited number of specifically regulated transcripts to discriminate perfectly among infecting pathogens in the training data. Validation trials using an algorithmic decision tree revealed 94.4% diagnostic accuracy when discerning the presence of bacterial infection. The model subsequently differentiated between bacterial pathogens with 71.4% accuracy and between non-bacterial conditions with 70.0% accuracy, both far exceeding the expected diagnostic yield of standard culture-based bronchoscopy with bronchoalveolar lavage. Conclusions: These data substantiate the specificity of the pulmonary innate immune response and support the feasibility of a gene expression-based clinical tool for pneumonia diagnosis.

Keywords: pathogen- and time-dependent host lung gene expression changes in pneumonia
 
Overall design Mouse lungs were removed 6 h after challenge with P. aeruginosa, S. pneumoniae, A. fumigatus or sham (PBS), RNA was collected from leukoreduced lung homogenates, then cRNA was amplified and hybridized to Illumina Sentrix mouse-6 gene expression arrays v1.1. Gene expression data was analyzed to determine if there were distinct patterns of host trasnscription that corresponded with a specific infection.
 
Contributor(s) Evans SE
Citation(s) 20653947
Submission date Apr 28, 2009
Last update date Jan 18, 2013
Contact name Scott E Evans
E-mail(s) seevans@mdanderson.org
Organization name University of Texas-M.D. Anderson Cancer Center
Department Pulmonary Medicine - Unit 1462
Street address 1400 Holcombe Blvd
City Houston
State/province TX
ZIP/Postal code 77030
Country USA
 
Platforms (1)
GPL6099 Illumina mouse-6 v1.0 expression beadchip
Samples (84)
GSM398342 4117185023_A [18h blinded; Pseudomonas infected]
GSM398343 4117185023_B [18h blinded; PBS exposed]
GSM398344 4117185023_C [18h blinded; Pseudomonas infected]
Relations
BioProject PRJNA116975

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
GSE15869_RAW.tar 4.3 Mb (http)(custom) TAR
GSE15869_rank_invariant_norm_18h_blinded.txt.gz 11.0 Mb (ftp)(http) TXT
GSE15869_rank_invariant_norm_18h_training.txt.gz 10.8 Mb (ftp)(http) TXT
GSE15869_rank_invariant_norm_2h_training.txt.gz 14.3 Mb (ftp)(http) TXT
GSE15869_rank_invariant_norm_6h_training.txt.gz 14.4 Mb (ftp)(http) TXT
GSE15869_unnormalized_18h_blinded.txt.gz 10.8 Mb (ftp)(http) TXT
GSE15869_unnormalized_18h_training.txt.gz 10.2 Mb (ftp)(http) TXT
GSE15869_unnormalized_2h_training.txt.gz 13.8 Mb (ftp)(http) TXT
GSE15869_unnormalized_6h_training.txt.gz 13.9 Mb (ftp)(http) TXT
Processed data included within Sample table
Processed data are available on Series record
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