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. 2019 Nov 18;9:16948. doi: 10.1038/s41598-019-53188-0

Figure 1.

Figure 1

Multi-Scale Multi-Paradigm Model Generation. Before this process, the model generates an average scalar equation by fitting the organism’s Pareto Front to experimental data using the ATP hydrolysis maintenance reaction as further elucidated in Methods. Then, starting from the top and progressing with the arrows (clockwise): The multi-objective Pareto Front is corrected for environmental variables and cellular preferences using a weighting algorithm and assuming a normally distributed cell biomass (more detail in Methods). The corrected biomass equation is solved, individually, for each cell subject to existing constraints, a steady state over each time step, an appropriate maintenance ATP flux, and a scalar objective function for which all coefficients add to one. This is interpreted using the agent-based model to make individual cell and physiological decisions including (1) whether the cell should die, (2) whether the cell should reproduce (and if it does, what type of cell does it differentiate into), and (3) how it should interact with the environment and other cells. These interactions inform the status of the other cells (using an intrafilamental diffusion mechanism) and the environment (modeled with the same diffusion mechanism for CO2, N2, organic, and fixed nitrogen products, and assuming excesses of other media components). The iteration restarts with the objective equation updating each living cell (whether newly reproduced or previously established) based on the cell’s current metabolic state.