In silico identification of NF-kappaB-regulated genes in pancreatic beta-cells

Background: Pancreatic beta-cells are the target of an autoimmune attack in type 1 diabetes mellitus (T1DM). This is mediated in part by cytokines, such as interleukin (IL)-1β and interferon (IFN)-γ. These cytokines modify the expression of hundreds of genes, leading to beta-cell dysfunction and death by apoptosis. Several of these cytokine-induced genes are potentially regulated by the IL-1β-activated transcription factor (TF) nuclear factor (NF)-κB, and previous studies by our group have shown that cytokine-induced NF-κB activation is pro-apoptotic in betacells. To identify NF-κB-regulated gene networks in beta-cells we presently used a discriminant analysis-based approach to predict NF-κB responding genes on the basis of putative regulatory elements. Results: The performance of linear and quadratic discriminant analysis (LDA, QDA) in identifying NF-κB-responding genes was examined on a dataset of 240 positive and negative examples of NFκB regulation, using stratified cross...

• Type: Journal
• Year: 2007
• Where: BMCBI
• Authors: Najib Naamane, Jacques van Helden, Decio L. Eizirik
• Keywords: Beta-cells, BMCBI 2007, NF-κB, Putative Target Genes