Systems-Level Analyses of the Mammalian Innate Immune Response

The regulation of the innate immune response, our first line of defence against infectious disease, does not involve simple linear pathways but rather complex inter-connected networks of interactions, regulatory loops, and multifaceted transcriptional responses. Given this complexity, systems biology approaches to investigate the host innate immune response are essential. InnateDB (www.innatedb.com) is a publicly available database and integrated analysis platform specifically designed to facilitate systems-level analyses of the mammalian innate immune response and is one of the most comprehensive databases of all human and mouse molecular interactions (130,000+) and pathways (3,000+). Building upon this, more than 12,900 innate immunity-relevant molecular interactions have been contextually annotated through detailed review of the literature providing novel insight into the innate immunity interactome. Integrated bioinformatics solutions include the ability to investigate user-supplied quantitative data in a network and pathway context using pathway, ontology and transcription factor over-representation analyses, and network visualisation and analysis tools. In this chapter, we introduce innate immunity as a complex system and a provide a detailed step-by-step guide to using InnateDB and other bioinformatics tools to investigate the host response to infectious disease.

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