From COVID-19 Disease Map Molecular Mechanisms to Executable Cell-specific Logical Models

The COVID-19 Disease Map project aims to map and explore the many molecular processes involved in SARS-CoV-2 infection. To represent and understand the complexity of the multicellular events triggered by this virus infection, the information gathered in this repository may be used to assemble and refine cell-specific logical models. Macrophages, being part of the innate immune system, are involved in the inflammatory response and are one of the cell types directly affected by the virus. Understanding the role of macrophages in the progression of viral infection may lead to new insights for treatments. A logical model of macrophage polarization developed recently at NTNU is now further enhanced using knowledge of the COVID-19 Disease Map and configured to represent the effects of SARS-CoV-2 drug treatments in a cell and pathogen-specific way. Curated signaling pathway mechanisms represented as molecular interaction diagrams in the COVID-19 Disease Map are converted and upgraded to meet Boolean modeling criteria and validated to ensure they specifically occur in macrophages. Also, adaptations to the macrophage polarization model are performed to represent the biological outcomes related to the disease (e.g., inflammatory response, phagocytosis, viral replication). Finally, these different modules are integrated into one Boolean model, and stable state analysis and drug perturbation simulations are performed. The results will provide insight into the biological processes affected in macrophages during acute COVID-19 infection and how treatment with specific drugs may alleviate the detrimental effects of viral infection. Our poster describes how to covidize a relevant cellular model and the steps that it takes to validate the disease model, and can be used to guide the development of multicellular models representing the COVID-19 disease.