%0 Journal Article
%T A module-based analytical strategy to identify novel disease-associated genes shows an inhibitory role for interleukin 7 Receptor in allergic inflammation
%A Reza Mobini
%A Bengt A Andersson
%A Jonas Erjef£żlt
%A Mirjana Hahn-Zoric
%A Michael A Langston
%A Andy D Perkins
%A Lars Cardell
%A Mikael Benson
%J BMC Systems Biology
%D 2009
%I BioMed Central
%R 10.1186/1752-0509-3-19
%X To test these hypotheses integrated analysis of a large number of gene expression microarray experiments from different forms of allergy was performed. This led to the identification of an experimentally validated reference gene that was used to construct a module of co-expressed and interacting genes. This module was validated in an independent material, by replicating the expression changes in allergen-challenged CD4+ cells. Moreover, the changes were reversed following treatment with corticosteroids. The module contained several novel disease-associated genes, of which the one with the highest number of interactions with known disease genes, IL7R, was selected for further validation. The expression levels of IL7R in allergen challenged CD4+ cells decreased following challenge but increased after treatment. This suggested an inhibitory role, which was confirmed by functional studies.We propose that a module-based analytical strategy is generally applicable to find novel genes in complex diseases.Most common diseases, including allergy and diabetes, are complex. The genetic susceptibility of an individual to such a disease appears not to be the result of a single causative gene but rather arises from multiple interacting genes. The identification of novel disease-associated genes is complicated not only by the large number of potentially relevant genes as well as the heterogeneity of the diseases. One approach to address this complexity is to arrange disease-associated genes in networks, where the genes form nodes and the interactions between the genes are represented by links between the nodes. Since disease genes tend to interact [1,2] the investigation may be facilitated by searching for sub-networks of co-expressed and interacting genes (such sub-networks will henceforth be referred to as modules). The rationale behind this is that in gene interaction networks, functionally related genes tend to form modules of tightly interacting genes [1,2]. Thus, such module
%U http://www.biomedcentral.com/1752-0509/3/19