Toward Scalable Whole-Cell Modeling of Human Cells.

ABSTRACTWhole-cell (WC) models comprehensively predict cellular phenotypes by simulating the biochemistry in individual cells. WC models have the potential to enable bioengineers and physicians to rationally design microorganisms and medical therapies. WC models are developed by combining multiple mathematically distinct pathway sub-models into a single multi-algorithm model. The only existing WC model represents a small bacterium. However, to enable medical therapy, new scalable methods are needed to model human cells that contain 100 times more molecular species and 10,000-100,000 times more molecules. We describe the design of a novel system for building and simulating WC models, including an expressive sequence- and rule-based modeling language and a multi-algorithm simulator that employs optimistic parallel discrete event simulation.