An introduction to whole-cell modeling

Despite extensive research into individual molecules and pathways, we still do not have a complete understanding of cell biology. To comprehensively understand cells, we must build whole-cell (WC) computational models that predict phenotype from genotype by representing all of the biochemical activity inside cells. In addition to helping researchers gain novel insights into biology, WC models could also help bioengineers design microorganisms and help physicians personalize medicine. Recently, we and others demonstrated that WC models are feasible by leveraging recent advances in computational and experimental technology to build the first model that represents every characterized gene in a cell. Although substantial work remains to develop comprehensive WC models, we believe that WC models can be achieved by systemizing cell modeling and coordinating the cell modeling community.

The goals of this primer are to teach researchers about the motivation, goals, principles, and methods of WC modeling and to prepare researchers to contribute to WC modeling. Toward this goal, the primer includes introductory readings and hands-on tutorials on WC modeling, the fundamental principles and methods of cell modeling, computer programming and software engineering, Linux computer systems, and scientific communication. Section 1 introduces the motivation, goals, and fundamental challenges of WC modeling; describes why WC modeling is becoming feasible; summarizes the principles and methods of WC modeling; reviews the latest WC models and their limitations; outlines the major bottlenecks to WC modeling; proposes a plan for achieving WC models as a community; and describes ongoing work to advance WC modeling. Section 2 introduces several foundational concepts and skills for WC modeling including computer programming, Linux computer systems, and scientific communication. Section 3 outlines the theoretical foundations for WC modeling. Section 4 describes the principles and methods of WC modeling. Section 5 outlines several funding opportunities for WC modeling.

Please note, this primer is under active development. Over time, we aim to develop a complete primer with detailed examples and tutorials. We welcome suggestions and feedback.