Rapid community-driven development of a SARS-CoV-2 tissue simulator

Yafei Wang; Randy Heiland; Morgan Craig; Courtney L. Davis; Ashlee N Ford Versypt; Adrianne Jenner; Jonathan Ozik; Nicholson Collier; Chase Cockrell; Andrew Becker; Gary An; James A. Glazier; Aarthi Narayanan; Amber M Smith; Paul Macklin

Custom functions can be attached to individual cell agents to model molecular-scale, intracellular processes and couple these with cell phenotypic parameters. These internal models are often implemented as systems of ODEs. For example, cell uptake of diffusing substrates can be coupled with a metabolism model (system ODEs), and the resulting energy output can be used to set the cell's cycle progression and necrotic death probability 93 . For small systems of ODEs, these models are coded "by hand" with standard finite difference techniques. More complex models are written in systems biology markup language (SBML) 94 These approaches will be used to assess (1) The CIABM is intended to be a generalizable model of CD8 dynamics, designed to represent different disease states resulting from different perturbations (i.e. specific infections of specific pathogens, putative vaccines and their administration strategy). This is consistent with our group's philosophy of pathophysiological unification through modeling. We have developed multiple ABMs related to the immune response and diseases related to inflammation and immune dysfunction 98, 99 , and will leverage this experience to integrate various aspects of these models as components of the CIABM. Many of these models are based on the IIRABM 98 , which is an abstract representation and simulation of the human inflammatory signaling network response to injury; the model has been calibrated such that it reproduces the general clinical trajectories seen in sepsis. The IIRABM operates by simulating multiple cell types and their interactions, including endothelial cells, macrophages, neutrophils, TH0, TH1, and TH2 cells as well as their associated precursor cells. The simulated system dies when total damage (defined as aggregate endothelial cell damage) exceeds 80%; this threshold represents the ability of current medical technologies to keep patients alive (i.e., through organ support machines) in conditions that previously would have been lethal. The IIRABM will be used in the CIABM to represent the innate and host tissue component of the CIABM.