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- Lopes, Miguel, et al.
(författare)
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Temporal profiling of cytokine-induced genes in pancreatic beta-cells by meta-analysis and network inference
- 2014
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Ingår i: Genomics. - : Elsevier BV. - 0888-7543 .- 1089-8646. ; 103:4, s. 264-275
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Tidskriftsartikel (refereegranskat)abstract
- Type I Diabetes (T1D) is an autoimmune disease where local release of cytokines such as IL-1 beta and IFN-gamma contributes to beta-cell apoptosis. To identify relevant genes regulating this process we performed a meta-analysis of 8 datasets of beta-cell gene expression after exposure to IL-1 beta and IFN-gamma. Two of these datasets are novel and contain time-series expressions in human islet cells and rat INS-1E cells. Genes were ranked according to their differential expression within and after 24 h from exposure, and characterized by function and prior knowledge in the literature. A regulatory network was then inferred from the human time expression datasets, using a time-series extension of a network inference method. The two most differentially expressed genes previously unknown in T1D literature (RIPK2 and ELF3) were found to modulate cytokine-induced apoptosis. The inferred regulatory network is thus supported by the experimental validation, providing a proof-of-concept for the proposed statistical inference approach.
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