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A module-based analytical strategy to identify novel disease-associated genes shows an inhibitory role for interleukin 7 Receptor in allergic inflammation

Mobini, Reza; Andersson, Bengt A.; Erjefält, Jonas LU ; Hahn-Zoric, Mirjana; Langston, Michael A.; Perkins, Andy D.; Cardell, Lars Olaf and Benson, Mikael (2009) In BMC Systems Biology 3.
Abstract
Background: The identification of novel genes by high-throughput studies of complex diseases is complicated by the large number of potential genes. However, since disease-associated genes tend to interact, one solution is to arrange them in modules based on co-expression data and known gene interactions. The hypothesis of this study was that such a module could be a) found and validated in allergic disease and b) used to find and validate one ore more novel disease-associated genes. Results: 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... (More)
Background: The identification of novel genes by high-throughput studies of complex diseases is complicated by the large number of potential genes. However, since disease-associated genes tend to interact, one solution is to arrange them in modules based on co-expression data and known gene interactions. The hypothesis of this study was that such a module could be a) found and validated in allergic disease and b) used to find and validate one ore more novel disease-associated genes. Results: 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. Conclusion: We propose that a module-based analytical strategy is generally applicable to find novel genes in complex diseases. (Less)
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author
organization
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type
Contribution to journal
publication status
published
subject
in
BMC Systems Biology
volume
3
publisher
BioMed Central
external identifiers
  • wos:000264392600001
  • scopus:62649129291
ISSN
1752-0509
DOI
10.1186/1752-0509-3-19
language
English
LU publication?
yes
id
a23dda3d-2977-4b72-bec0-c204f22ffab3 (old id 1401920)
date added to LUP
2009-06-03 14:25:55
date last changed
2017-02-05 03:47:09
@article{a23dda3d-2977-4b72-bec0-c204f22ffab3,
  abstract     = {Background: The identification of novel genes by high-throughput studies of complex diseases is complicated by the large number of potential genes. However, since disease-associated genes tend to interact, one solution is to arrange them in modules based on co-expression data and known gene interactions. The hypothesis of this study was that such a module could be a) found and validated in allergic disease and b) used to find and validate one ore more novel disease-associated genes. Results: 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. Conclusion: We propose that a module-based analytical strategy is generally applicable to find novel genes in complex diseases.},
  author       = {Mobini, Reza and Andersson, Bengt A. and Erjefält, Jonas and Hahn-Zoric, Mirjana and Langston, Michael A. and Perkins, Andy D. and Cardell, Lars Olaf and Benson, Mikael},
  issn         = {1752-0509},
  language     = {eng},
  publisher    = {BioMed Central},
  series       = {BMC Systems Biology},
  title        = {A module-based analytical strategy to identify novel disease-associated genes shows an inhibitory role for interleukin 7 Receptor in allergic inflammation},
  url          = {http://dx.doi.org/10.1186/1752-0509-3-19},
  volume       = {3},
  year         = {2009},
}