A functional and regulatory map of asthma.
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 systems-level 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 high-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-beta1 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.
Novershtern
Noa
N
School of Computer Science and Engineering, Faculty of Medicine, The Hebrew University, Jerusalem.
Itzhaki
Zohar
Z
Manor
Ohad
O
Friedman
Nir
N
Kaminski
Naftali
N
D000465:Algorithms; D000485:Allergens; D000818:Animals; D001249:Asthma / Q000235:genetics* / Q000276:immunology* / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D004195:Disease Models, Animal; D020869:Gene Expression Profiling; D006801:Humans; D006967:Hypersensitivity; D007113:Immunity, Innate; D018793:Interleukin-13 / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008805:Mice, Inbred A; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D018345:Mice, Knockout; D008954:Models, Biological; D020411:Oligonucleotide Array Sequence Analysis; D010047:Ovalbumin; D025941:Protein Interaction Mapping; D015203:Reproducibility of Results; D049490:Systems Biology; D014158:Transcription, Genetic; D053773:Transforming Growth Factor beta1 / Q000502:physiology*
D000485:Allergens; D018793:Interleukin-13; D053773:Transforming Growth Factor beta1; D010047:Ovalbumin