A Functional and Regulatory Map of Asthma

Noa Novershtern, Zohar Itzhaki, Ohad Manor, Nir Friedman, Naftali Kaminski
2008 American Journal of Respiratory Cell and Molecular Biology  
The prevalence and morbidity of asthma, a chronic inflammatory airway disease, is increasing. Animal models provide a meaningful but limited view of the mechanisms of asthma in humans. A systemslevel view of asthma that integrates multiple levels of molecular and functional information is needed. For this, we compiled a gene expression compendium from five publicly available mouse microarray datasets and a gene knowledge base of 4,305 gene annotation sets. Using this collection we generated a
more » ... gh-level map of the functional themes that characterize animal models of asthma, dominated by innate and adaptive immune response. We used Module Networks analysis to identify co-regulated gene modules. The resulting modules reflect four distinct responses to treatment, including early response, general induction, repression, and IL-13-dependent response. One module with a persistent induction in response to treatment is mainly composed of genes with suggested roles in asthma, suggesting a similar role for other module members. Analysis of IL-13-dependent response using protein interaction networks highlights a role for TGF-b1 as a key regulator of asthma. Our analysis demonstrates the discovery potential of systems-level approaches and provides a framework for applying such approaches to asthma.
doi:10.1165/rcmb.2007-0151oc pmid:17921359 pmcid:PMC2258452 fatcat:5q34aozwa5gs3gznrnzdo5quzu