A Multi-Scale Modelling Framework of the Whole Human Body Based on Multi-Objective Functions

Abstract

Constraint-based multi-scale metabolic models are powerful tools to study complex biological systems like the human body, and to develop new treatment strategies for human diseases. They capture different scales of the system under study and provide the opportunity of understanding the interaction between multiple scales. In this paper, we have used our previously developed multi-scale whole body metabolism framework to establish a new approach to include multiple objectives of the human cells in computational analysis. The model has 3555 ordinary differential equations (ODEs) integrated with a genome-scale model of the hepatocyte, including 1826 biochemical reactions. The model has been solved for 74 objective functions simultaneously. Simulation results show that the integration algorithm has promise with respect to convergence, computational efficiency and response to perturbation. The results suggest that this method holds significant potential for the simulation of the range of metabolic phenotypes for mammalian cells where there are multiple objectives.