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Title: Host lung gene expression patterns predict the etiology of infectious pneumonias      
availability:
available
aggregation:
instance of dataset
privacy:
not applicable
refinement:
curated
dateReleased:
06-10-2011
ID:
E-GEOD-15869
description:
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 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.
keywords:
transcription profiling by array
format:
HTML
storedIn:
Array Express
qualifier:
not compressed
accessType:
landing page
authorization:
none
authentication:
none
primary:
true
accessURL: https://www.ebi.ac.uk/arrayexpress/experiments/E-GEOD-15869
format:
JSON
storedIn:
OmicsDI
qualifier:
not compressed
accessType:
download
authorization:
none
authentication:
none
primary:
false
accessURL: www.omicsdi.org/ws/dataset/arrayexpress-repository/E-GEOD-15869.json
format:
XML
storedIn:
OmicsDI
qualifier:
not compressed
accessType:
download
authorization:
none
authentication:
none
primary:
false
accessURL: http://www.omicsdi.org/ws/dataset/arrayexpress-repository/E-GEOD-15869.xml
ID:
SCR:014747
name:
Omics Discovery Index
abbreviation:
OmicsDI
homePage: http://www.omicsdi.org/