An elucidation of the regulation of the Interferon pathway using the <em>Interferome</em> and <em>Enrich</em> bioinformatics resources. — ASN Events
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  3. An elucidation of the regulation of the Interferon pathway using the Interferome and Enrich bioinformatics resources.

An elucidation of the regulation of the Interferon pathway using the Interferome and Enrich bioinformatics resources. (#230)

Sam Forster 1 , Ross Chapman 1 , Helen Cumming 1 , Alex Finkel 1 , Jamie Gearing 1 , Kevin Luu 1 , David Hughes 1 , Paul Hertzog 1
  1. Centre for Innate Immunity & Infectious Diseases, MIMR-PHI, Monash University, Clayton, Victoria, Australia

Aims

Interferons play a vital role in mammalian responses to bacterial and viral infections and to tumor development. The Interferon response following disease challenge is highly modulated. The host response must be sufficient to protect the host, but excessive responses can cause toxicity and even death. Furthermore, the Interferon response follows a highly structured temporal response, with stimulation activating an organised sequence of transcriptomic events. Here we present two bioinformatics tools that can be used to analyse the transcriptional regulation of the Interferon response: 1) the Interferome v2.0 database (http://interferome.its.monash.edu.au/interferome/home.jspx), which identifies genes regulated by Interferons from mouse and human systems, and 2) the Enrich custom software, which is powerful and intuitive tool for identifying transcription factors involved in regulating co-expressed gene sets and thus elucidating signaling pathways.

Methods

The Interferome database was queried for genes that were up-regulated in murine cells over discrete time periods following stimulation by type I Interferons. Transcription factors that were significantly enriched (p<0.05) among each gene set were identified using the Enrich custom bioinformatics tool.

Results

Interrogation of the Interferome database identified hundreds of genes that are up-regulated following stimulation by type I Interferon at different time points. Following analysis of the associated promoters using Enrich, we have been able to identify clear patterns in the transcription factors associated with temporally co-expressed genes. Many of the transcription factors identified are already known to be involved in the Interferon pathway, such as STATs and IRFs. However, the analysis also revealed the involvement of further additional transcription factors which might provide new insights into Interferon signalling.

Conclusion

By integrating the Interferome and Enrich bioinformatics resources, it has been possible to explore the transcription factors that regulate different phases of the interferon response. The analysis has identified new regulatory elements for experimental validation.