Abstract
BackgroundWhile technological advances have made it possible to profile the immune system at high resolution, translating high-throughput data into knowledge of immune mechanisms has been challenged by the complexity of the interactions underlying immune processes. Tools to explore the immune network are critical for better understanding the multi-layered processes that underlie immune function and dysfunction, but require a standardized network map of immune interactions. To facilitate this we have developed ImmunoGlobe, a manually curated intercellular immune interaction network extracted from Janeway’s Immunobiology textbook.ResultsImmunoGlobe is the first graphical representation of the immune interactome, and is comprised of 253 immune system components and 1112 unique immune interactions with detailed functional and characteristic annotations. Analysis of this network shows that it recapitulates known features of the human immune system and can be used uncover novel multi-step immune pathways, examine species-specific differences in immune processes, and predict the response of immune cells to stimuli. ImmunoGlobe is publicly available through a user-friendly interface at www.immunoglobe.org and can be downloaded as a computable graph and network table.ConclusionWhile the fields of proteomics and genomics have long benefited from network analysis tools, no such tool yet exists for immunology. ImmunoGlobe provides a ground truth immune interaction network upon which such tools can be built. These tools will allow us to predict the outcome of complex immune interactions, providing mechanistic insight that allows us to precisely modulate immune responses in health and disease.
Highlights
The immune system is composed of a complex network of cells [1], receptors [2, 3]and secreted molecules [4], and an effective immune response requires coordination across these many components [3, 5, 6]
Individual systems immunology approaches have been successful in several cases, for example in elucidating the immune networks involved in inflammation by using cytokine secretion profiles to create mathematical models of immune cell interactions [12] and inferring the immune networks that define tumor immunogenicity using genomic and transcriptomic data [13]
To provide meaningful results network analysis tools must be based upon a network map that is highly accurate, in order to correctly represent the underlying biology, and detailed, in order to provide interpretable insights into immune mechanisms
Summary
The immune system is composed of a complex network of cells [1], receptors [2, 3]and secreted molecules [4], and an effective immune response requires coordination across these many components [3, 5, 6]. Individual systems immunology approaches have been successful in several cases, for example in elucidating the immune networks involved in inflammation by using cytokine secretion profiles to create mathematical models of immune cell interactions [12] and inferring the immune networks that define tumor immunogenicity using genomic and transcriptomic data [13]. These types of systems immunology studies largely involve personalized analysis pipelines which require high levels of specialized analytical expertise to design and run, making them inaccessible to most researchers. To facilitate this we have developed ImmunoGlobe, a manually curated intercellular immune interaction network extracted from Janeway’s Immunobiology textbook
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