ImmCellFIE: producing high-resolution snapshots of the functions of immune cells

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ABSTRACT The immune system comprises a multitude of major cell types, each of which have unique functions. Understanding these diverse functions is fundamental to unraveling the immune system’s role in combating infectious disease, cancer development, autoimmune diseases, and chronic inflammation. The Immunology Database and Analysis Portal (ImmPort) currently shares data from 391 immunology studies, allowing further analysis by the immunology community. Integrating ImmPort data with additional community tools and data can increase the reach and impact of this high-value resource. To facilitate deeper and more mechanistic insights into the molecular basis of immunological functions, systems biology communities have created and validated computational models and algorithms that can accurately elucidate and quantify the functions of a cell based on analyses of omics data. Our computational toolbox, called CellFIE (Cell Function InferencE), does this by using complex systems biology models to first define modules of genes that work together to accomplish specific cell functions, and then overlaying omics data on these gene modules to infer changes in the activities of these functions in any given sample. The initial implementation of CellFIE has successfully quantified the scale of known metabolic functions for many different cell types, and differentiated functions of immune cell types. Consequently, we propose to expand CellFIE beyond metabolism to capture the synthesis and/or secretion of cytokines and membrane receptors involved in immune cell function. We will also adapt CellFIE to capture functions of specific signaling pathways. To make this computational toolbox and other omics analysis tools accessible and intuitive to researchers globally, we will develop ImmCellFIE, a sustainable, extensible, and usable software package and data repository built on Findable, Accessible, Interoperable and Reusable (FAIR) principles. Importantly, ImmCellFIE will include a web-enabled portal, intuitive visualizations, easy-to-use programmable interfaces for integrating omics data from various immunological databases, and the database annotations resulting from the ImmCellFIE secondary analyses. In this way, we will democratize the complicated systems biology analyses. The metabolic, secretory, and signaling phenotype annotations enabled by an intuitive dashboard and cyberinfrastructure that can easily integrate external data sources and systems will broaden the reach of omics data in ImmPort, other databases, and novel experiments. ImmCellFIE will harness these complex data to unravel detailed mechanisms in immunology research and beyond.